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Tag: Stem Cells

  • 10th Annual Regenerative Medicine Essentials Course and World Stem Cell Summit Return to Live with Virtual Option in 2023

    10th Annual Regenerative Medicine Essentials Course and World Stem Cell Summit Return to Live with Virtual Option in 2023

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    Newswise — WINSTON-SALEM, NC, February 9, 2023 – The Wake Forest Institute for Regenerative Medicine (WFIRM) and the Regenerative Medicine Foundation (RMF) have announced the 20th edition of World Stem Cell Summit will be held in conjunction with the 10th annual Regenerative Medicine Essentials Course, uniquely formatted this year for both in person and virtual attendance from June 5-9, 2023.

    Produced by the non-profit RMF, and in its 20th year, the World Stem Cell Summit is the most inclusive and expansive interdisciplinary, networking, and partnering meeting in the stem cell science and regenerative medicine field. With the overarching purpose of fostering translation of biomedical research, funding, and investments targeting cures, the Summit and co-located Course serve a diverse ecosystem of stakeholders and influencers.

    From the science behind pioneering discoveries and clinical applications, to regulatory and manufacturing challenges, the Summit and the Course will provide a comprehensive look at progress to date, current challenges, new “hot” topics as well as future applications.

    The World Stem Cell Summit is the educational and networking focal point for scientists, business leaders, regulators, policy-makers, patient advocates, economic development officers, experts in law and ethics, and visionary gurus from around the world since 2003. The Regenerative Medicine Essentials Course, taught by prominent experts, features a foundational instruction into the field of regenerative medicine, with examination on the structure and function of damaged tissues and organs. 

    Joint single-track programming for the Summit and the Course – the “official course” of RMF – will be held at Wake Forest locations in the Innovation Quarter located in downtown Winston-Salem. Course founder and WFIRM Director Anthony Atala, M.D., serves as co-director with Joan Schanck, MPA, WFIRM’s Chief Education Program Officer, and RMF Executive Director Bernard Siegel, JD.

    “We welcome the World Stem Cell Summit and RMF’s partnership on this venture,” Atala said. “RMF and Bernard Siegel have provided critical leadership to the field for more than 20 years, as a catalyst for the formation of valuable collaborations, while focusing upon patient advocacy, public policy issues, advancing funding initiatives, workforce development and worldwide public awareness.”

    According to Schanck, the program is designed for clinicians, researchers, technicians, students, industry, investors and government representatives. Topics include stem cells, biomaterials, cell therapies, clinical trials, regulatory matters, pathways to market, bio-manufacturing technologies and much more.

    “The Summit and Course showcase the entire regenerative medicine ecosystem and will provide timely information to expand knowledge and provide quality solutions to deliver effective treatments and cures, sooner rather than later – all in a spirit of friendship and cooperation,” Siegel said. “In the next weeks, WFIRM and RMF will announce the strategic partners and institutions supporting this event that will reach a global audience.”

    AlphaMed Press and Stem Cells Translational Medicine, the official journal partner of RMF, endorse the Course and the Summit.

    For more information about the upcoming virtual World Stem Cell Summit, please visit: www.worldstemcellsummit.com. To receive the latest information about the RME schedule, speakers and topics, bookmark this page.

     

     

     

    About Wake Forest Institute for Regenerative Medicine: WFIRM is recognized as an international leader in translating scientific discovery into clinical therapies, with many world firsts, including the development and implantation of the first engineered organ in a patient. Over 400 people at the institute, the largest in the world, work on more than 40 different tissues and organs. A number of the basic principles of tissue engineering and regenerative medicine were first developed at the institute. WFIRM researchers have successfully engineered replacement tissues and organs in all four categories – flat structures, tubular tissues, hollow organs and solid organs – and 16 different applications of cell/tissue therapy technologies, such as skin, urethras, cartilage, bladders, muscle, kidney, and vaginal organs, have been successfully used in human patients. The institute, which is part of Wake Forest School of Medicine, is located in the Innovation Quarter in downtown Winston-Salem, NC, and is driven by the urgent needs of patients. The institute is making a global difference in regenerative medicine through collaborations with over 400 entities and institutions worldwide, through its government, academic and industry partnerships, its start-up entities, and through major initiatives in breakthrough technologies, such as tissue engineering, cell therapies, diagnostics, drug discovery, biomanufacturing, nanotechnology, gene editing and 3D printing. 

    About RegenMed Development Organization: The mission of the RegenMed Development Organization (ReMDO) is to accelerate the discovery and translation of regenerative medicine therapies. ReMDO is a 501(c)3 non-profit organization that manages a clinical translation initiative that includes thought leaders, representatives from leading US research centers, government representatives, and companies of all sizes. ReMDO conducts research to de-risk technologies and speed up their translation to clinical practice and to the global market. ReMDO manages the world’s first and only professional organization dedicated solely to advancing the regenerative medicine field, the Regenerative Medicine Manufacturing Society (RMMS), and the Regenerative Medicine Manufacturing Innovation Consortium (RegMIC), which manages a private-public partnership of industry and academic members focused on scaling up technologies.

    About the World Stem Cell Summit: The World Stem Cell Summit is a project of the nonprofit Regenerative Medicine Foundation. Since 2003, Regenerative Medicine Foundation has built the strongest, most comprehensive and trusted global network for Regenerative Medicine, uniting the world’s leading researchers, medical centers, universities, labs, businesses, funders, policymakers, experts in law, regulation and ethics, medical philanthropies and patient organizations. Our mission is to accelerate regenerative medicine to improve health and deliver cures. We are committed to the ethical advancement of an innovative medicine powered by regenerative, restorative, and curative technologies. All we do is in service of health, life, and the alleviation of human suffering.

    About the Regenerative Medicine Foundation: The nonprofit Regenerative Medicine Foundation fosters strategic collaborations to accelerate the development of regenerative medicine to improve health and deliver cures. RMF unites the world’s leading researchers, medical centers, universities, labs, businesses, funders, policymakers, experts in law, regulation and ethics, medical philanthropies, and patient organizations. We maintain a trusted network of leaders and pursue our mission by producing our flagship World Stem Cell Summit series of conferences and public days, honoring leaders through the Stem Cell and Regenerative Medicine Action Awards, supporting our official journal partner STEM CELLS Translational Medicine (SCTM), promoting solution-focused policy initiatives both nationally and internationally and creating STEM/STEAM educational projects. For more information about RMF, please visit: www.regmedfoundation.org.

     

     

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    Wake Forest Institute for Regenerative Medicine

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  • SYF2 suppression mitigates neurodegeneration in models of diverse forms of ALS

    SYF2 suppression mitigates neurodegeneration in models of diverse forms of ALS

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    Reducing levels of a spliceosome-associated factor, SYF2, attenuates TDP-43 pathology in models of diverse forms of ALS. Therefore, these findings by Linares et al. indicate that SYF2 suppression may function as a broadly acting therapeutic strategy for the treatment of ALS.

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    Cell Stem Cell

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  • From grave to cradle: Collagen-induced gut cell reprogramming

    From grave to cradle: Collagen-induced gut cell reprogramming

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    Newswise — Tokyo, Japan – Most cells have a pretty normal life: they’re born, they grow, they get old, and they die. But the Benjamin Buttons of the cellular world can go from old to young again in the right context. Now, researchers from Japan have identified a physical cue that sparks this change in cells in the human gut.

    In a study published this month in Inflammation and Regeneration, researchers from Tokyo Medical and Dental University (TMDU) have revealed that the accumulation of a thick, extracellular material called collagen at injured sites in the gut stimulates cellular reprogramming.

    When the intestine is injured, an inflammatory response occurs that is often associated with regeneration of the injured tissues. This process involves converting some mature intestinal cells back into fetal-like cells that can then generate new healthy tissue to repair the injured area.

    “We previously showed that deposition of collagen at the site of intestinal injury promotes the conversion of intestinal/colonic epithelial cells covering the wound bed towards fetal-like progenitors in mice,” says lead author of the study, Sakurako Kobayashi. “However, the detailed mechanism by which this occurs, and whether this process also occurs in humans, remained unclear.”

    To explore these questions, the researchers created collagen spheres, which are tiny balls of epithelial cells grown in purified collagen, from mouse and human intestinal cells. They then assessed gene expression in these spheres to clarify the mechanisms of inflammation-associated reprogramming.

    “The results showed that culturing in collagen induced the expression of inflammation-associated and fetal-like genes in both human and mouse intestinal cells,” explains Shiro Yui, senior author. “As previously reported, the YAP/TAZ-TEAD axis definitely plays a central role in the induction of this distinctive gene expression signature, but this time we identified the cooperative transcriptional activity of Fra1 and RUNX2 in the process, which hammers the gene network centered on Fibronectin.”

    Importantly, the representative genes that were activated in the human collagen spheres were also highly expressed in tissue samples taken from inflamed regions of the gut in patients with ulcerative colitis.

    “Taken together, our findings demonstrate that collagen has a significant influence on inflammation and cellular reprogramming in both mice and humans,” says Kobayashi.

    Given that some of the genes that were upregulated in the collagen spheres are also overexpressed in conditions such as colorectal cancer, it is possible that there is a link between the regenerative cascade and colorectal carcinogenesis. Thus, investigating the mechanisms of cell fate conversion using this model may enhance our understanding not only of how inflammation is influenced by the extracellular environment, but also how other disease processes occur in the gut.

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    The article, “Collagen type I‑mediated mechanotransduction controls epithelial cell fate conversion during intestinal inflammation,” was published in Inflammation and Regeneration at DOI: 10.1186/s41232-022-00237-3

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    Tokyo Medical and Dental University

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  • Dry eye disease alters how the eye’s cornea heals itself after injury

    Dry eye disease alters how the eye’s cornea heals itself after injury

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    Newswise — People with a condition known as dry eye disease are more likely than those with healthy eyes to suffer injuries to their corneas. Studying mice, researchers at Washington University School of Medicine in St. Louis have found that proteins made by stem cells that regenerate the cornea may be new targets for treating and preventing such injuries.

    The study is published online Jan. 2 in the Proceedings of the National Academy of Sciences.

    Dry eye disease occurs when the eye can’t provide adequate lubrication with natural tears. People with the common disorder use various types of drops to replace missing natural tears and keep the eyes lubricated, but when eyes are dry, the cornea is more susceptible to injury.

    “We have drugs, but they only work well in about 10% to 15% of patients,” said senior investigator Rajendra S. Apte, MD, PhD, the Paul A. Cibis Distinguished Professor in the John F. Hardesty, MD, Department of Ophthalmology & Visual Sciences. “In this study involving genes that are key to eye health, we identified potential targets for treatment that appear different in dry eyes than in healthy eyes. Tens of millions of people around the world — with an estimated 15 million in the United States alone — endure eye pain and blurred vision as a result of complications and injury associated with dry eye disease, and by targeting these proteins, we may be able to more successfully treat or even prevent those injuries.”

    The researchers analyzed genes expressed by the cornea in several mouse models — not only of dry eye disease, but also of diabetes and other conditions. They found that in mice with dry eye disease, the cornea activated expression of the gene SPARC. They also found that higher levels of SPARC protein were associated with better healing.

    “We conducted single-cell RNA sequencing to identify genes important to maintaining the health of the cornea, and we believe that a few of them, particularly SPARC, may provide potential therapeutic targets for treating dry eye disease and corneal injury,” said first author Joseph B. Lin, an MD/PhD student in Apte’s lab.

    “These stem cells are important and resilient and a key reason corneal transplantation works so well,” Apte explained. “If the proteins we’ve identified don’t pan out as therapies to activate these cells in people with dry eye syndrome, we may even be able to transplant engineered limbal stem cells to prevent corneal injury in patients with dry eyes.”

    Lin JB, Shen X, Pfeifer CW, Shiau F, Santeford A, Ruzycki PA, Clark BS, Liu Q, Huang AJW, Apte RS. Dry eye disease in mice activates adaptive corneal epithelial regeneration distinct from constitutive renewal in homeostasis. Proceedings of the National Academy of Sciences, Jan. 2, 2023.

    The study was funded with support from the National Eye Institute, the National Institute of Diabetes and Digestive and Kidney Diseases and the National Institute of General Medical Sciences of the National Institutes of Health (NIH). Grant numbers: R01 EY019287, R01 EY027844, R01 EY024704, P30 EY02687, F30 DK130282, T32 GM07200 Additional funding provided by the Jeffrey T. Fort Innovation Fund, a Centene Corp. contract for the Washington University-Centene ARCH Personalized Medicine Initiative and Research to Prevent Blindness.

    About Washington University School of Medicine

    WashU Medicine is a global leader in academic medicine, including biomedical research, patient care and educational programs with 2,700 faculty. Its National Institutes of Health (NIH) research funding portfolio is the fourth largest among U.S. medical schools, has grown 54% in the last five years, and, together with institutional investment, WashU Medicine commits well over $1 billion annually to basic and clinical research innovation and training. Its faculty practice is consistently within the top five in the country, with more than 1,790 faculty physicians practicing at over 60 locations and who are also the medical staffs of Barnes-Jewish and St. Louis Children’s hospitals of BJC HealthCare. WashU Medicine has a storied history in MD/PhD training, recently dedicated $100 million to scholarships and curriculum renewal for its medical students, and is home to top-notch training programs in every medical subspecialty as well as physical therapy, occupational therapy, and audiology and communications sciences.

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    Washington University in St. Louis

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  • Barriers to mesenchymal stromal cells for low back pain

    Barriers to mesenchymal stromal cells for low back pain

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    Intervertebral disc degeneration is the main cause of low back pain. In the past 20 years, the injection of mesenchymal stromal cells (MSCs) into the nucleus pulposus of the degenerative disc has become the main approach for the treatment of low back pain. Despite the progress made in this field, there are still many barriers to overcome. First, intervertebral disc is a highly complex load-bearing composite tissue composed of annulus fibrosus, nucleus pulposus and cartilaginous endplates. Any structural damage will change its overall biomechanical function, thereby causing progressive degeneration of the entire intervertebral disc. Therefore, MSC-based treatment strategies should not only target the degenerated nucleus pulposus but also include degenerated annulus fibrosus or cartilaginous endplates. Second, to date, there has been relatively little research on the basic biology of annulus fibrosus and cartilaginous endplates, although their pathological changes such as annular tears or fissures, Modic changes, or Schmorl’s nodes are more commonly associated with low back pain. Given the high complexity of the structure and composition of the annulus fibrosus and cartilaginous endplates, it remains an open question whether any regeneration techniques are available to achieve their restorative regeneration. Finally, due to the harsh microenvironment of the degenerated intervertebral disc, the delivered MSCs die quickly. Taken together, current MSC-based regenerative medicine therapies to regenerate the entire disc complex by targeting the degenerated nucleus pulposus alone are unlikely to be successful.

    Core Tip: Intervertebral disc is a highly complex weight-bearing tissue, and its degeneration is a major cause of low back pain. Current mesenchymal stromal cell-based clinical trials are difficult to succeed because the repair only targets the degenerated nucleus pulposus, and the transplanted cells die rapidly.

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    World Journal of Stem Cells

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  • SPOC domain-containing protein 1 regulates the proliferation and apoptosis of human spermatogonial stem cells through adenylate kinase 4

    SPOC domain-containing protein 1 regulates the proliferation and apoptosis of human spermatogonial stem cells through adenylate kinase 4

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    BACKGROUND

    Spermatogonial stem cells (SSCs) are the origin of male spermatogenesis, which can reconstruct germ cell lineage in mice. However, the application of SSCs for male fertility restoration is hindered due to the unclear mechanisms of proliferation and self-renewal in humans.

    AIM

    To investigate the role and mechanism of SPOC domain-containing protein 1 (SPOCD1) in human SSC proliferation.

    METHODS

    We analyzed publicly available human testis single-cell RNA sequencing (RNA-seq) data and found that SPOCD1 is predominantly expressed in SSCs in the early developmental stages. Small interfering RNA was applied to suppress SPOCD1 expression to detect the impacts of SPOCD1 inhibition on SSC proliferation and apoptosis. Subsequently, we explored the target genes of SPOCD1 using RNA-seq and confirmed their role by restoring the expression of the target genes. In addition, we examined SPOCD1 expression in some non-obstructive azoospermia (NOA) patients to explore the correlation between SPOCD1 and NOA.

    RESULTS

    The uniform manifold approximation and projection clustering and pseudotime analysis showed that SPOCD1 was highly expressed in the early stages of SSC, and immunohistological results showed that SPOCD1 was mainly localized in glial cell line-derived neurotrophic factor family receptor alpha-1 positive SSCs. SPOCD1 knockdown significantly inhibited cell proliferation and promoted apoptosis. RNA-seq results showed that SPOCD1 knockdown significantly downregulated genes such as adenylate kinase 4 (AK4). Overexpression of AK4 in SPOCD1 knockdown cells partially reversed the phenotypic changes, indicating that AK4 is a functional target gene of SPOCD1. In addition, we found a significant downregulation of SPOCD1 expression in some NOA patients, suggesting that the downregulation of SPOCD1 may be relevant for NOA.

    CONCLUSION

    Our study broadens the understanding of human SSC fate determination and may offer new theories on the etiology of male infertility.

    Core Tip: In this study, we reported the dominant expression of SPOC domain-containing protein 1 (SPOCD1) in human spermatogonial stem cells (SSCs). Knockdown of SPOCD1 in SSC caused a significant decrease in proliferation and self-renewal, and the induction of apoptosis. RNA sequencing showed that SPOCD1 knockdown caused significant downregulation of genes such as adenylate kinase 4 (AK4), and overexpression of AK4 in SPOCD1-knockdown cells reversed the phenotypic alterations induced by SPOCD knockdown. Additionally, we found significant downregulation of SPOCD1 in non-obstructive azoospermia patients. These results broaden our understanding of human SSC fate determination and provide new theories on the etiology of male infertility.

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    World Journal of Stem Cells

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  • Optimal concentration of mesenchymal stem cells for fracture healing in a rat model with long bone fracture

    Optimal concentration of mesenchymal stem cells for fracture healing in a rat model with long bone fracture

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    BACKGROUND

    There is still no consensus on which concentration of mesenchymal stem cells (MSCs) to use for promoting fracture healing in a rat model of long bone fracture.

    AIM

    To assess the optimal concentration of MSCs for promoting fracture healing in a rat model.

    METHODS

    Wistar rats were divided into four groups according to MSC concentrations: Normal saline (C), 2.5 × 106 (L), 5.0 × 106 (M), and 10.0 × 106 (H) groups. The MSCs were injected directly into the fracture site. The rats were sacrificed at 2 and 6 wk post-fracture. New bone formation [bone volume (BV) and percentage BV (PBV)] was evaluated using micro-computed tomography (CT). Histological analysis was performed to evaluate fracture healing score. The protein expression of factors related to MSC migration [stromal cell-derived factor 1 (SDF-1), transforming growth factor-beta 1 (TGF-β1)] and angiogenesis [vascular endothelial growth factor (VEGF)] was evaluated using western blot analysis. The expression of cytokines associated with osteogenesis [bone morphogenetic protein-2 (BMP-2), TGF-β1 and VEGF] was evaluated using real-time polymerase chain reaction.

    RESULTS

    Micro-CT showed that BV and PBV was significantly increased in groups M and H compared to that in group C at 6 wk post-fracture (P = 0.040, P = 0.009; P = 0.004, P = 0.001, respectively). Significantly more cartilaginous tissue and immature bone were formed in groups M and H than in group C at 2 and 6 wk post-fracture (P = 0.018, P = 0.010; P = 0.032, P = 0.050, respectively). At 2 wk post-fracture, SDF-1, TGF-β1 and VEGF expression were significantly higher in groups M and H than in group L (P = 0.031, P = 0.014; P < 0.001, P < 0.001; P = 0.025, P < 0.001, respectively). BMP-2 and VEGF expression were significantly higher in groups M and H than in group C at 6 wk post-fracture (P = 0.037, P = 0.038; P = 0.021, P = 0.010). Compared to group L, TGF-β1 expression was significantly higher in groups H (P = 0.016). There were no significant differences in expression levels of chemokines related to MSC migration, angiogenesis and cytokines associated with osteogenesis between M and H groups at 2 and 6 wk post-fracture.

    CONCLUSION

    The administration of at least 5.0 × 106 MSCs was optimal to promote fracture healing in a rat model of long bone fractures.

    Core Tip: This study focused on the optimal concentration of mesenchymal stem cells (MSCs) that affect fracture healing in a rat model of long bone shaft fracture. Factors related to the homing effect of MSCs, osteogenesis and angiogenesis were analyzed by in vivo (radiographic and histologic evaluation) as well as in vitro (reverse transcriptase-polymerase chain reaction and western blot analysis). Among the various concentrations used, the administration of at least 5.0 × 106 MSCs was optimal to promote the therapeutic effect on fracture healing.

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    World Journal of Stem Cells

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  • Biomaterial application strategies to enhance stem cell-based therapy for ischemic stroke

    Biomaterial application strategies to enhance stem cell-based therapy for ischemic stroke

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    BACKGROUND

    Ischemic stroke is a condition in which an occluded blood vessel interrupts blood flow to the brain and causes irreversible neuronal cell death. Transplantation of regenerative stem cells has been proposed as a novel therapy to restore damaged neural circuitry after ischemic stroke attack. However, limitations such as low cell survival rates after transplantation remain significant challenges to stem cell-based therapy for ischemic stroke in the clinical setting. In order to enhance the therapeutic efficacy of transplanted stem cells, several biomaterials have been developed to provide a supportable cellular microenvironment or functional modification on the stem cells to optimize their reparative roles in injured tissues or organs.

    AIM

    To discuss state-of-the-art functional biomaterials that could enhance the therapeutic potential of stem cell-based treatment for ischemic stroke and provide detailed insights into the mechanisms underlying these biomaterial approaches.

    METHODS

    The PubMed, Science Direct and Scopus literature databases were searched using the keywords of “biomaterial” and “ischemic stroke”. All topically-relevant articles were then screened to identify those with focused relevance to in vivo, in vitro and clinical studies related to “stem cells” OR “progenitor cells” OR “undifferentiated cells” published in English during the years of 2011 to 2022. The systematic search was conducted up to September 30, 2022.

    RESULTS

    A total of 19 articles matched all the inclusion criteria. The data contained within this collection of papers comprehensively represented 19 types of biomaterials applied on seven different types of stem/progenitor cells, namely mesenchymal stem cells, neural stem cells, induced pluripotent stem cells, neural progenitor cells, endothelial progenitor cells, neuroepithelial progenitor cells, and neuroblasts. The potential major benefits gained from the application of biomaterials in stem cell-based therapy were noted as induction of structural and functional modifications, increased stem cell retention rate in the hostile ischemic microenvironment, and promoting the secretion of important cytokines for reparative mechanisms.

    CONCLUSION

    Biomaterials have a relatively high potential for enhancing stem cell therapy. Nonetheless, there is a scarcity of evidence from human clinical studies for the efficacy of this bioengineered cell therapy, highlighting that it is still too early to draw a definitive conclusion on efficacy and safety for patient usage. Future in-depth clinical investigations are necessary to realize translation of this therapy into a more conscientious and judicious evidence-based therapy for clinical application.

    Core Tip: Ischemic stroke is becoming a significant health issue globally. An increasing number of studies have proposed the applications of regenerative stem cells for the treatment of this neurodegenerative disease. We critically reviewed the literature on biomaterial application to enhance the therapeutic potential of stem/progenitor cell therapy for ischemic stroke. Despite the limited evidence collected to translate this evidence into clinical practice, it is postulated that application of stem cells as regenerative treatment for stroke is practicable and beneficial for stroke patients, especially those in the chronic phase of stroke which could not be cured by any other established means.

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    World Journal of Stem Cells

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  • Experimental Cancer Therapy Shows Success in More Than 70 Percent of Patients in Global Clinical Trials

    Experimental Cancer Therapy Shows Success in More Than 70 Percent of Patients in Global Clinical Trials

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    Newswise — New York, NY (December 10, 2022) — A new therapy that makes the immune system kill bone marrow cancer cells was successful in as many as 73 percent of patients in two clinical trials, according to researchers from The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai.

    The therapy, known as a bispecific antibody, binds to both T cells and multiple myeloma cells and directs the T cells—white blood cells that can be enlisted to fight off diseases—to kill multiple myeloma cells. The researchers described this strategy as “bringing your army right to the enemy.”

    The success of the off-the-shelf immunotherapy, called talquetamab, was even seen in patients whose cancer was resistant to all approved multiple myeloma therapies. It uses a different target than other approved therapies: a receptor expressed on the surface of cancer cells known as GPRC5D.

    Talquetamab was tested in phase 1 and phase 2 trials. The phase 1 trial, which was reported in The New England Journal of Medicine (NEJM), established two recommended doses that were tested in the Phase 2 trial. The results of the Phase 2 trial were reported at the American Society of Hematology annual meeting on Saturday, December 10. The study participants had all been previously treated with at least three different therapies without achieving lasting remission, suggesting talquetamab could offer new hope for patients with hard-to-treat multiple myeloma.

     “This means that almost three-quarters of these patients are looking at a new lease on life,” said Ajai Chari, MD, Director of Clinical Research in the Multiple Myeloma Program at The Tisch Cancer Institute and lead author of both studies. “Talquetamab induced a substantial response among patients with heavily pretreated, relapsed, or refractory multiple myeloma, the second-most-common blood cancer. It is the first bispecific agent targeting the protein GPRC5d in multiple myeloma patients.”

    Nearly all patients with myeloma who receive standard therapies continually relapse. Patients who relapse or become resistant to all approved multiple myeloma therapies have a poor prognosis, so additional treatments are urgently needed. This study, while an early-phase trial designed to detect tolerability and find a safe dose, is an important step in meeting that need.

    This Phase 1 clinical trial enrolled 232 patients at several cancer centers across the world between January 2018 and November 2021. Patients received a variety of doses of the therapy either intravenously or injected under their skin; future studies will focus on doses only administered under the skin either weekly or every other week

    The efficacy and safety findings in the phase 1 study were validated in the phase 2 trial presented at ASH. The phase 2 trial included 143 patients treated on a weekly dose and 145 patients treated at a higher biweekly dose.

    The overall response rate in these two groups was about 73 percent, Dr. Chari said. The response rate was maintained throughout various subgroups examined, with the exception of patients with a rare form of multiple myeloma that also extends to organs and soft tissues. More than 30 percent of patients in both groups had a complete response (no detection of myeloma-specific markers) or better, and nearly 60 percent had a “very good partial response” or better (indicating the cancer was substantially reduced but not necessarily down to zero).

    The median time to a measurable response was approximately 1.2 months in both dosing groups and the median duration of response to date is 9.3 months with weekly dosing. Researchers are continuing to collect data on the duration of response in the group receiving 0.8 mg/kg every other week and for patients in both dosing groups who had a complete response or better.

    Side effects were relatively frequent, but typically mild. About three-quarters of patients experienced cytokine release syndrome, which is a constellation of symptoms including fever that is common with immunotherapies. About 60 percent experienced skin-related side effects such as rash, about half reported taste changes, and about half reported nail disorders. The researchers said very few patients (5 to 6 percent) stopped talquetamab treatment because of side effects.

    The response rate observed in the study, which Dr. Chari explained is higher than that for most currently accessible therapies, suggests talquetamab could offer a viable option for patients whose myeloma has stopped responding to most available therapies, offering a chance to extend life and benefit from other new and future therapies as they are developed.

    These trials were sponsored and funded by Janssen.

      

    About the Mount Sinai Health System

    Mount Sinai Health System is one of the largest academic medical systems in the New York metro area, with more than 43,000 employees working across eight hospitals, over 400 outpatient practices, nearly 300 labs, a school of nursing, and a leading school of medicine and graduate education. Mount Sinai advances health for all people, everywhere, by taking on the most complex health care challenges of our time — discovering and applying new scientific learning and knowledge; developing safer, more effective treatments; educating the next generation of medical leaders and innovators; and supporting local communities by delivering high-quality care to all who need it.

    Through the integration of its hospitals, labs, and schools, Mount Sinai offers comprehensive health care solutions from birth through geriatrics, leveraging innovative approaches such as artificial intelligence and informatics while keeping patients’ medical and emotional needs at the center of all treatment. The Health System includes approximately 7,300 primary and specialty care physicians; 13 joint-venture outpatient surgery centers throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and more than 30 affiliated community health centers. We are consistently ranked by U.S. News & World Report‘s Best Hospitals, receiving high “Honor Roll” status, and are highly ranked: No. 1 in Geriatrics and top 20 in Cardiology/Heart Surgery, Diabetes/Endocrinology, Gastroenterology/GI Surgery, Neurology/Neurosurgery, Orthopedics, Pulmonology/Lung Surgery, Rehabilitation, and Urology. New York Eye and Ear Infirmary of Mount Sinai is ranked No. 12 in Ophthalmology. U.S. News & World Report’s “Best Children’s Hospitals” ranks Mount Sinai Kravis Children’s Hospital among the country’s best in several pediatric specialties. The Icahn School of Medicine at Mount Sinai is one of three medical schools that have earned distinction by multiple indicators: It is consistently ranked in the top 20 by U.S. News & World Report‘s “Best Medical Schools,” aligned with a U.S. News & World Report “Honor Roll” Hospital, and top 20 in the nation for National Institutes of Health funding and top 5 in the nation for numerous basic and clinical research areas. Newsweek’s “The World’s Best Smart Hospitals” ranks The Mount Sinai Hospital as No. 1 in New York and in the top five globally, and Mount Sinai Morningside in the top 20 globally.

    For more information, visit https://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.

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    Mount Sinai Health System

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  • Penn Medicine Researchers Present Advance in Re-Treatment with CAR T Therapy

    Penn Medicine Researchers Present Advance in Re-Treatment with CAR T Therapy

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    Newswise — NEW ORLEANS –  Researchers from the University of Pennsylvania’s Abramson Cancer Center presented preliminary results of an ongoing Phase I clinical trial demonstrating successful re-treatment with CAR T cell therapy for patients whose cancers relapsed after previous CAR T therapy at the 2022 American Society of Hematology (ASH) Annual Meeting (Abstract 2016).

    CAR T therapies have revolutionized blood cancer treatment over the last decade, providing hope for patients who have run out of conventional treatment options, but patients whose cancers return or stop responding to CAR T therapy have limited options for further treatment.

    The first-in-human study (NCT04684563) evaluated a novel fourth-generation CAR T therapy in patients with non-Hodgkin lymphoma (NHL) who had previously received CAR T therapy that failed to stop their cancer. The study is the first clinical trial in the United States with anti-CD19 CAR T cells secreting interleukin 18 (IL 18). The early results show this combination approach is safe and did not result in new or increased side effects compared to other commercially available CAR T therapies. 

    Senior author and CAR T pioneer Carl June, MD, led the preclinical research that demonstrated IL18 could enhance CAR T activity. “We designed an ‘armored’ CAR that secretes IL18 and tested it in mice, where we found it to have potent antitumor efficacy in our preclinical studies,” said June, who is the Richard W. Vague Professor in Immunotherapy in the department of Pathology and Laboratory Medicine in the Perelman School of Medicine and director of the Center for Cellular Immunotherapies at Penn’s Abramson Cancer Center.

    Among the first seven patients who received huCART19-IL18 – including those who previously did not respond to or relapsed following treatment with commercial CAR T cell therapies – all responded to the therapy (four patients had a complete response and three patients had a partial response). None of the four patients whose cancers completely responded to treatment at month three have seen their disease return, and all patients are alive at a median follow-up of eight months.

    “Patients whose cancers don’t respond or become refractory to CAR T therapy tend to have poor outcomes, so we are very motivated to find new options for them,” said lead author Jakub Svoboda, MD, an associate professor of Hematology-Oncology at Penn. “Although these are preliminary results, it’s encouraging to see how well these patients have done.  Our team at Penn is very excited about this ongoing project and these early results continue to motivate us.”

    The study enrolled patients with CD19+ relapsed/refractory NHL or chronic lymphocytic leukemia (CLL), who had received at least two lines of therapy, including CAR T therapy. The study is continuing to increase the dose of huCART19-IL18 and will enroll patients one at a time until the appropriate dose is determined.

    Toxicities related to huCART19-IL18 were temporary and similar to those which have been observed with other CAR T products. Cytokine release syndrome occurred in four patients and neurotoxicity occurred in two patients. No grade four adverse events or study-related deaths have occurred.

    Notably, with a three-day manufacturing time, huCART19-IL18 can be ready to administer more quickly than CAR T products with the typical manufacturing time of nine to 14 days, which is especially important for patients with aggressive, fast-growing disease. A previous, preclinical study found the shortened manufacturing time also may enhance the potency of the T cells.

    Svoboda will present the abstract in a poster session on Saturday, Dec. 10 from 5:30 to 7:30 p.m. CT in Hall D.   

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    Perelman School of Medicine at the University of Pennsylvania

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  • Fred Hutch at ASH: Global insights on AML outcomes, COVID-19 and cancer, CD19 CAR T-cell therapy updates, latest on precision oncology — and more

    Fred Hutch at ASH: Global insights on AML outcomes, COVID-19 and cancer, CD19 CAR T-cell therapy updates, latest on precision oncology — and more

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    Newswise — SEATTLE — Dec. 1, 2022 — The 64th Annual Meeting and Exposition of the American Society of Hematology (ASH) will take place virtually and in person Dec. 10-13 in New Orleans, Louisiana.

    Below are highlights of Fred Hutchinson Cancer Center research to be presented, and you can follow Fred Hutch updates on Twitter #ASH22. You can also check out Fred Hutch’s booth 2622 in the exhibit hall.

    This year’s ASH press program highlights work below by Fred Hutch:

    Poster presentation: An analysis of the worldwide utilization of hematopoietic stem cell transplantation for acute myeloid leukemia Abstract: 3638 Presenter: Molly Tokaz Other Fred Hutch authors: Andrew Cowan and Mary-Beth Percival Sunday, Dec. 11, 6 p.m.

    A global study of use of transplantation for acute myeloid leukemia led by Fred Hutch fellow Dr. Molly Tokaz will be featured in a Dec. 7 virtual-only ASH briefing, “Building Solutions to Challenges in Health Equity.”

    Late-breaking session: Zanubrutinib demonstrates superior progression-free survival (PFS) compared with ibrutinib for treatment of relapsed/refractory chronic lymphocytic leukemia and small lymphocytic lymphoma (R/R CLL/SLL): Results from final analysis of ALPINE randomized phase 3 study Abstract: LBA-6 Senior author: Mazyar Shadman (On Twitter: @mshadman) Tuesday, Dec. 13, 8:30 a.m.

    A Dec. 12 media briefing on late-breaking abstracts will include an abstract co-authored by Fred Hutch’s Dr. Mazyar Shadman, a chronic lymphocytic leukemia and lymphoma physician-investigator. The abstract gives an update on a clinical trial assessing a next-generation Bruton tyrosine kinase inhibitor.

    Also on the press program, Dr. Stephanie Lee, former president of ASH, will moderate the Dec. 10 briefing “New Drugs, New Targets.” Dr. Lee is a transplant physician-scientist and expert in chronic graft-vs.-host-disease and holds the David and Patricia Giuliani/Oliver Press Endowed Chair in Cancer Research at Fred Hutch.

    Learn more in the ASH Annual Meeting press program.

    Poster presentation: Timing of PD-L1 Blockade with Durvalumab May Affect Outcomes of CD19 CAR-T Cell Therapy for Relapsed/Refractory Large B-Cell Lymphoma Abstract: 3316 Presenter: Alexandre Hirayama (On Twitter: @xanira) Sunday, Dec. 11, 6 p.m.

    Adding checkpoint blockades may make CAR T-cell therapy more effective against blood cancers, but combination trial results so far have been disappointing. This clinical trial evaluates the importance of timing of the therapies.

    Poster presentation: CAR T-cell therapy for relapsed or refractory large B-cell lymphoma using a fully human CD10-targeted single chain variable fragment: Results of a first-in-human phase I/II study Abstract: 4654 Presenter: Nicolas Gazeau (On Twitter: @NGazeau14) Monday, Dec. 12, 6 p.m.

    CAR T-cell therapies targeting the marker CD19 on cancer cells achieve high response rates in patients with relapsed or refractory large B-cell lymphoma, but durable responses are only achieved in 30-40% of patients. Based on clinical evidence showing lack of a durable response linked to a mouse-based component of the engineered cell, a phase I/II clinical trial is evaluating the effectiveness of the CAR T rebuilt with a human-based component instead. 

    Poster presentation: 3-Year follow-up analysis of ZUMA-5: a Phase 2 study of axicabtagene ciloleucel (Axi-Cel) in patients with relapsed/refractory (R/R) indolent non-hodgkin lymphoma (iNHL)

    Abstract: 4660 Co-author: David Maloney Monday Dec. 12, 6 p.m.

    This is a 3-year follow-up of the ZUMA-5 study, which shows that the CAR T-cell therapy called axi-cel demonstrated continued durable responses in patients with relapsed/refractory indolent non-hodgkin’s lymphoma (R/R iNHL) with improved survival observed in patients with marginal zone lymphoma. Late progression or death due to lymphoma or study treatment were uncommon and no new safety signals arose since the 2-year analysis. The research team also looked at biomarkers related to outcomes and found that preinfusion immunosuppressive Treg-related biomarkers were associated with relapse in patients with follicular lymphoma.

    Poster presentation: Circulating tumor DNA in untreated classical hodgkin lymphoma patients treated with pembrolizumab and chemotherapy: Dynamic response assessment and correlation with baseline metabolic tumor volume

    Abstract: 2913 Presenter: Ryan Lynch Sunday, Dec. 11, 6 p.m.

    This abstract presents updated results of a Fred Hutch single-center investigator-initiated clinical trial of the checkpoint inhibitor called pembrolizumab plus a chemotherapy for untreated classical Hodgkin lymphoma. The researchers continued to demonstrate a favorable safety profile with excellent efficacy (median follow up of 2.1 years, 2-year progression free survival of 97%). They also present new correlative data with circulating tumor DNA (ctDNA) for detection of minimal residual disease. It is possible that immunotherapy combinations may be associated with increased rates of uptake of residual F-fluorodeoxyglucose, which is a nonspecific imaging agent, and the team found that many of these patients have not had their cancer come back even several years later. In contrast, ctDNA was able to identify the lack of ctDNA clearance in the only patient who has relapsed today despite favorable initial PET scans. These findings indicate that ctDNA may represent a more sensitive and specific response assessment tool to be studied in larger datasets.

    Oral presentation: Self-reported experiences of adult hematopoietic cell transplantation survivors with COVID-19 vaccination and infection Abstract: 378 Presenter: Emily Liang (On Twitter: @emilyliangmd) Saturday, Dec. 10, 5:15 p.m.

    In a report of about 1700 stem cell transplant survivors, Fred Hutch clinicians found that vaccinated patients and their household contacts had a lower rate of COVID-19 infection compared with unvaccinated individuals (patients: 6% vs 68%, or 10-fold lower rate of infection; household contacts: 10% vs 46%, or 4-fold lower rate of infection) and were more likely to take additional safety precautions including masking and social distancing. The Fred Hutch team hopes the findings encourage others to receive the COVID-19 vaccination given the protective effect of vaccination and low rates of vaccine-related side effects.

    Poster presentation: A risk model for CML patients with COVID-19: Importance of molecular response in the context of age, comorbidities and country income Abstract: 4327 Presenter: Jerry Radich Monday, Dec. 12, 6 p.m.

    Researchers on the iCMLf CANDID study, a collaboration of 157 centers from 58 countries and with nearly 700 chronic myeloid leukemia patients participating, are looking for risk factors to predict which people with chronic myeloid leukemia are more likely to suffer worse outcomes from COVID-19. Dr. Jerry Radich, who holds the Kurt Enslein Endowed Chair at Fred Hutch, will report on the group’s findings, which show that age, molecular aspects of an individual’s CML, comorbidities and wealth of countries impact COVID-19 outcomes in CML patients.

    Oral presentation: Anti-leukemic activity of STRO-002 a novel folate receptor-α (FR-α)-targeting ADC in relapsed/refractory CBF2AT3-GLIS2 AML Abstract: 66 Presenter: Soheil Meshinchi Saturday, Dec. 10, 10:45 a..m.

    Acute myeloid leukemia remains one of the most difficult to treat pediatric cancers. Physician-scientist Dr. Soheil Meshinchi has led efforts to characterize the biology of this cancer in young patients and to identify targeted treatments that best suit their specific disease. At ASH, he will give an update on one such treatment, which was tested as part of Project Stella at Fred Hutch. His hope is that with detailed molecular testing of each patient followed by a targeted therapy, that children with the disease will go on to live long and healthy lives.

    Poster presentation: Umbrella trial in myeloid malignancies: The myeloMATCH national clinical trials network precision medicine initiative Abstract: 4080 Co-author: Jerry Radich Monday, Dec. 12, 6 p.m.

    Fred Hutch is part of an initiative led by the National Cancer Institute to help people newly diagnosed with acute myeloid leukemia and myelodysplastic syndromes to have a rapid (less than 3 days) testing of the clinical and molecular makeup of their disease and then be matched with treatment trials with promising therapeutic combinations. Fred Hutch, under the leadership of Dr. Jerry Radich, has been chosen to coordinate and perform the diagnostic and monitoring aspects of this nationwide initiative.

    Oral session: Allogeneic transplantation: Acute and chronic GVHD, immune reconstitution: Clinical studies exploring the immunobiology of HCT Abstract: 722 Moderator: Kate Markey (On Twitter: @katemarkey) Saturday, Dec. 10, 9:30 a.m.

    New insights – bolstered by emerging technological breakthroughs – on how the immune system recovers following transplantation are increasing our understanding of post-transplant complications like graft-versus-host disease. Fred Hutch’s Dr. Kate Markey, a physician-scientist and expert on how the microbiome affects recovery from transplantation, will moderate this session that includes clinical data from groups exploring T cell recovery after transplantation and clinical reports.

    Poster presentation: HSCs engraft in a stochastic pattern and form clonal pools following transplantation Abstract: 2527 Presenter: Stefan Radtke Sunday, Dec. 11, 6 p.m.

    Previous Fred Hutch studies discovered a subtype of hematopoietic stem cells that give rise to all other cells in the blood and immune systems, which could be a powerful therapeutic target. But because the cells are so rare, they’ve been difficult to study. Findings in this poster used a new type of bar coding to track individual cells and reveal some of the cellular dynamics that underlie their regenerative abilities.

    Poster presentation: Clinical and functional implications of MYC variants as a new class of pathogenic variants in AML Abstract: 1472 Presenter: Danielle Kirkey Saturday, Dec. 10, 5:30 p.m.

    Understanding the underlying genetics of pediatric acute myeloid leukemia can help determine how best to treat this difficult to treat disease. One of the genetic players is MYC, an oncogene involved in a majority of human cancers. In this work, Fred Hutch researchers defined the presence of different MYC variants and found that some occur in about 3.5% of pediatric patients with AML. The team did additional analyses to link MYC variants with other previously known high-risk features of AML and found those associations to be linked to clinical outcomes, which will allow for more nuanced stratification of a patient’s risk and will help determine optimal treatment regimens.

    Oral presentation: Treatment patterns and outcomes of patients with primary or secondary acute myeloid leukemia by type of site (academic or community government): A CONNECT® Myeloid Registry Study

    Abstract: 4023 Presenter: Bart Scott Monday, Dec 12, 6 p.m.

    This research was conducted to better understand management of secondary acute myeloid leukemias (SAML), which is a type of blood cancer that starts in white blood cells that grow in the bone marrow, often affecting people who have one of these blood cell diseases: myelodysplastic syndrome (MDS), myeloproliferative disorder (MPD) and aplastic anemia. The Fred Hutch team evaluated treatment patterns and outcomes in patients enrolled in the CONNECT® Myeloid Disease Registry. The findings indicate that outcomes for patients with AML in the registry are consistent with previously reported outcomes. This analysis suggests that contrary to commonly held perceptions, site of care does not affect overall patient outcomes. The clinically meaningful increase in overall survival in patients receiving an allogeneic hematopoietic stem cell transplant, regardless of primary or secondary AML further emphasizes the importance of providing patients with the opportunity for transplant.

    Poster presentation: Clinical outcome and treatment-related mortality in patients with acute myeloid leukemia treated at the Uganda Cancer Institute

    Abstract: 4031 Presenter: Clement Dove Okello Co-author: Soheil Meshinchi Monday, Dec 12, 6 p.m.

    A retrospective review of acute myeloid leukemia outcomes at the Uganda Cancer Institute examined factors associated with treatment-related mortality. Treatment of AML is similar across countries, but treatment-related mortality is significantly greater in low-income countries compared with high-income countries. This study by UCI and Fred Hutch researchers examined factors that could be contributing to greater mortality, in hopes of improving outcomes. Through the UCI-Fred Hutch Collaboration, Dr. Soheil Meshinchi, a Fred Hutch expert in AML, advised on the project.

    Poster presentation: Revised prognostic index for patients with acute myeloid leukemia and other high-grade myeloid neoplasms in first relapse

    Abstract: 1385 Presenter: Noam E. Kopmar Saturday, Dec 10, 5:30 p.m.

    Though many patients with acute myeloid leukemia will achieve a first complete remission, most patients will relapse. Fred Hutch researchers looked at predictors of relapse and examined methods to create an improved risk stratification model that will better predict likelihood of a second complete remission and overall survival after relapse. Through a better understanding of prognosis, providers may improve their ability to determine the optimal treatment approach and also better inform the counseling provided to patients regarding prognosis.

    Poster presentation: Prognostic significance of chromosomal genomic array testing in adults with newly diagnosed acute lymphoblastic leukemia

    Abstract: 4145 Presenter: Noam E. Kopmar Saturday, Dec 12, 6 p.m.

    This project led by members of the acute leukemia and myeloid malignancies research group at Fred Hutch is aimed at improving prognostic capabilities at the time of either a new diagnosis or at the time of first relapse, correlating chromosomal genomic array testing results with key demographic and outcomes data. Having a better understanding of prognosis may improve the ability of providers to determine the optimal treatment approach and also better inform the counseling that is provided to patients regarding prognosis.

    The disease-killing T cells of the immune system develop their capabilities in a small, butterfly-shaped gland in the chest called the thymus. The thymus can regenerate to keep its immune function strong, but it wears out from stress, infection and aging. At ASH, Fred Hutch researchers will report their latest findings on how to repair the thymus:

    Oral presentation: Interleukin-18 suppresses regeneration of the thymus

    Abstract: 483 Presenter: David Granadier Co-author Jarrod Dudakov (On Twitter: @Dudakov_Lab) Monday, Dec 12, 4:30 p.m.

    Research by graduate student David Granadier in Dr. Jarrod Dudakov’s lab implicates the cytokine IL-18 in regulating the ability of the thymus to repair itself. This presentation will these latest insights. More on the signaling pathways involved in thymic regeneration and their implications for therapeutics in a Fred Hutch news story.

    Poster presentation: The zinc-sensing receptor GPR39 is a master regulator of immune reconstitution after bone marrow transplant in the thymus and in the bone marrow

    Abstract: 4581 Presenter: Lorenzo Iovino Co-author Jarrod Dudakov (On Twitter: @Dudakov_Lab) Monday, Dec 12, 6 p.m.

    Zinc is well-known for its immune-boosting properties, and recently Dr. Lorenzo Iovino in Dudakov’s lab at Fred Hutch revealed how zinc supports immune function through the thymus. Iovino will give an update on the work and how it could be used to improve treatments for cancer patients.

    Note: Fred Hutch and the scientists who contributed to these discoveries may stand to benefit from their future commercialization.

    The clinical trials referenced above involve investigational products and/or therapies that have not been approved for commercial marketing by the U.S. Food and Drug Administration or any other regulatory authority. Results may vary and encouraging results from early stage clinical trials may not be supported in later stage clinical trials.  No conclusions should be drawn from the information in this report about the safety, efficacy, or likelihood of regulatory approval of these investigational products and/or therapies.

    # # #

    Fred Hutchinson Cancer Center unites comprehensive care and advanced research to provide the latest cancer treatment options and accelerate discoveries that prevent, treat and defeat cancer and infectious diseases worldwide.

    Based in Seattle, Fred Hutch is an independent, nonprofit organization and the only National Cancer Institute-designated cancer center in Washington. We have earned a global reputation for our track record of discoveries in cancer, infectious disease and basic research, including important advances in bone marrow transplantation, HIV/AIDS prevention, immunotherapy and COVID-19 vaccines. Fred Hutch operates eight clinical care sites that provide medical oncology, infusion, radiation, proton therapy and related services and has network affiliations with hospitals in four states. Fred Hutch also serves as UW Medicine’s cancer program.

    Please note that our organization was renamed Fred Hutchinson Cancer Center in April 2022, following the merger of long-time partners, Fred Hutchinson Cancer Research Center and Seattle Cancer Care Alliance. 

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    Fred Hutchinson Cancer Center

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  • UC San Diego Awarded $8M to Expand Stem Cell Therapy Clinical Trials

    UC San Diego Awarded $8M to Expand Stem Cell Therapy Clinical Trials

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    Newswise — Stem cells show particular promise in treating diseases for which few other effective treatments exist. In these therapies, stem cells are introduced into the body where they develop into specialized cells that repair, restore, replace or regenerate cells that have been damaged by the disease.

    As part of a state-wide effort to advance stem cell therapies, the California Institute for Regenerative Medicine (CIRM) has awarded $8 million to the UC San Diego Alpha Stem Cell Clinic. The funding will support the clinic’s mission of bringing new stem cell-based therapies to patients with difficult-to-treat diseases.

    The Alpha Clinics — named for being the first of their kind — are a network of clinics spanning the state of California, designed to bridge the gap between stem cell research and clinical application. The system brings together clinical, research, regulatory and administrative teams in order to expedite clinical trials and streamline the patient experience.

    “We’re trying to change the way we do medicine,” said Catriona Jamieson, MD, PhD, director of the UC San Diego Alpha Stem Cell Clinic and chief of the Division of Regenerative Medicine at UC San Diego School of Medicine. “The Alpha Clinic helps academic and industry experts join forces to bring world-class technologies directly to the patients.”

    The grant is part of a series of recent CIRM awards totaling $72 million to expand the Alpha Clinics network. UC San Diego was one of three founding institutions when the project launched in 2015. The new funding will expand the program to nine sites across the state.

    In the seven years since its inception, the UC San Diego Alpha Stem Cell Clinic has launched 59 clinical trials and treated 277 patients with new therapies for neurodegeneration, diabetes and various forms of cancer. The trials largely test cell, gene and immunotherapies developed through growing partnerships between UC San Diego and local biotechnology and pharmaceutical companies.

    Recent milestones include the completion of a Phase I trial using neural stem cells to treat spinal cord injury, in which patients showed improved motor function after the treatment, as well as approval from the U.S. Food and Drug Administration (FDA) for a Phase III registration trial of a blood cancer stem cell-targeting monoclonal antibody.

    The latest funding will help expand clinical trials at both La Jolla and Hillcrest Medical Centers and create a Clinical Fellowship Program to educate additional physicians in advanced regenerative medicine therapies.

    Another major goal of the clinic is to improve accessibility and awareness of stem cell science. A portion of the funding will go towards new patient education programs and efforts to make treatments more accessible to historically underserved communities in San Diego and Imperial Counties.

    “Patients come to us when nothing else has worked, so we are thrilled to be able to provide new treatments to our community that are not available in other parts of the country,” said Jamieson. “The Alpha Clinics’ highly collaborative infrastructure will help us develop and validate high-quality stem cell therapies at an unprecedented speed, and the effects will be seen across California and beyond.”

    Funding for the UC San Diego Alpha Stem Cell Clinic comes from the California Institute for Regenerative Medicine (grant INFR4-13597).

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    University of California San Diego

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  • Is Cord-Blood Banking Worth It?

    Is Cord-Blood Banking Worth It?

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    In the fall of 1988, Matthew Farrow, a 5-year-old boy with a rare blood disorder, received the world’s first transplant of umbilical-cord blood from a newborn sibling. It worked: Farrow was cured. This miraculous outcome broke open a whole new field in medicine—and, not long after, a whole new industry aimed at getting expecting parents to bank their baby’s umbilical-cord blood, just in case.

    These days, in fact, being pregnant means being bombarded at the doctor’s office and on Instagram with ads touting cord blood as too precious to waste. For several hundred dollars upfront, plus a storage fee of $100 to $200 every year, the banks’ ads proclaim, you could save your child’s life. Cord-blood banking has been likened to a “biological insurance policy.”

    In the U.S., the two biggest private cord blood banks are Cord Blood Registry and ViaCord. Together, they have collected more than 1 million units. But only a few hundred units of this privately banked cord blood have ever been used in transplant, the great majority by families who chose to bank because they already had a child with a specific and rare disorder treatable with transplant. For everyone else, the odds of using privately banked cord blood are minuscule—so minuscule that the American Academy of Pediatrics (AAP) recommends against private banking. It does make an exception for families with that disease history. “But that’s a rare circumstance,” says Steve Joffe, a pediatric oncologist and ethicist at the University of Pennsylvania, “and not one that anybody is going to build a successful business model around.”

    ViaCord and Cord Blood Registry do offer free services for families in which someone has already been diagnosed with a condition treatable with cord blood. In general, the companies reiterated to me, cord blood does save lives and they are simply providing an option for families who want it.

    But the marketing also gives the impression of much more expansive uses for cord blood. The private banks’ websites list nearly 80 diseases treatable with transplant—an impressive number, though many are extremely uncommon or closely related to one another. (For example: refractory anemia, refractory anemia with ringed sideroblasts, refractory anemia with excess blasts, refractory anemia with excess blasts in transformation.) They have also recently taken to highlighting the promise of still-unproven treatments: Temporary infusions of cord blood, they say, could eventually treat more common conditions such as cerebral palsy and autism. Video testimonials feature parents talking excitedly about the potential of cord blood for their children. But the evidence isn’t there yet—and may never appear. Nonetheless, says Paul Knoepfler, a stem-cell scientist at UC Davis, “the cord-blood companies seem to be trying to expand their base of potential customers.”

    The initial exuberance around cord blood came from a real place. The blood left over in umbilical cords is replete with cells that have the special ability to turn into any kind of blood, including red blood cells, which carry oxygen, and white blood cells, which make up the immune system. Adults have stem cells in their bone marrow and blood—which can also be used for transplant—but those in a baby’s umbilical cord are more immunologically naive. That means they are less likely to go awry and attack a recipient’s body. “They don’t cause as much havoc,” says Karen Ballen, an oncologist at the University of Virginia. This allows doctors to use cord blood that matches only four out of six immunological markers.

    Because cord blood is so valuable, publicly run banks have been collecting donations since the 1990s. Despite amassing fewer units overall, public banks worldwide have provided 30 times as many units of blood for treatment—and saved more lives—than private ones, because they are accessible by any patient in need. Although the AAP recommends against private banking, it does recommend donating to public banks.

    One appeal of private banking, though, as the companies highlight, is that the cells in a baby’s umbilical cord are a perfect match for them in later childhood or adulthood. But this is usually irrelevant: In most of the diseases that can be cured by a cord-blood transplant, doctors would, for medical reasons, not use the patient’s own cells. In cases of inherited disorders such as sickle cell anemia, for example, a child’s own cord-blood stems have the same problematic mutation. For children with one of many types of leukemia, the concern is that cord blood could contain leukemia-precursor cells that cause the cancer to reappear; in addition, donor blood-stem cells are better because they can mop up remaining leukemia cells. Doctors would “never” use banked cord blood from a child with these types of leukemia, says Joanne Kurtzberg, a pediatrician and cord-blood pioneer at Duke University, who helped treat Farrow when he was a young boy.

    When privately banked cord blood is used in transplants, it is more likely to go to a sibling. Genetically, siblings have about a 25 percent chance of being perfect matches for each other. The chances of finding a suitable match among unrelated bone-marrow or cord-blood donors from a public bank, on the other hand, range from 29 to 79 percent, depending on one’s ethnic background. (The majority of donors are white, so it’s highest for white patients.) In any case, not banking a matched sibling’s cord blood doesn’t foreclose the possibility of a transplant, because that sibling can still donate bone marrow. “I often encounter families who have some guilt around not storing the cord blood, and I will point out, ‘Well, your donor child that matches our patient is still here,’” says Ann Haight, a pediatric hematologist and oncologist at Emory University.

    Even if a baby’s cord blood is banked, there’s no guarantee that it will contain enough cells for transplant. In fact, most may not: Public banks only keep 5 to 40 percent of their donations, as the rest don’t meet their standards. Private banks will save much smaller samples, which they argue serve a different purpose. Whereas public banks are looking for large samples that are mostly likely to be used for transplant, says Kate Giradi, the director of medical and scientific affairs at ViaCord, “when families are banking with us, this is that child’s only cord, so our threshold is way lower.”

    Another reason to bank these smaller samples, a spokesperson for Cord Blood Registry pointed out, is that they can still be used for experimental infusions treating conditions such as cerebral palsy and autism. (About 80 percent of units released by CBR have been used this way, as have about half from ViaCord.) The private banks partner with researchers, such as Kurtzberg at Duke, who are running clinical trials to test these treatments. The theory goes that cells from cord blood can make it to the brain, where they might have some neuroprotective role—but the mechanism remains unknown, and the effects are not entirely clear. As Kurtzberg told me, “The therapy is not proven.”

    The current state of cord-blood science might be summed up thus: Proven uses are very uncommon, and unproven uses are, well, unproven. Of course, a future discovery could lead to a real breakthrough in the use of stem cells from cord blood—an idea private banks trade on. Who knows what might be in store for cord blood later, when your baby is 30, 50, 70 years old? In a recent Cord Blood Registry survey of new parents, a spokesperson told me by email, 45 percent named “belief in future treatments” as the primary reason for banking their child’s cord blood and tissue. Knoepfler, the stem-cell scientist, notes that scientists have been excited for decades about the promise of stem cells. But translating interesting results in the lab to a doctor’s office, he says, “​​is really much harder than many of us realized. I include myself in that.”

    Medical discoveries have actually changed the ways cord blood is used over years, but they have so far resulted in less use of cord blood. In the past several years, doctors have refined a protocol to use half-matched donors in transplants. Doctors generally get more cells from these donors than from an infant’s banked cord blood, which means the transplants “take” more quickly and the patient spends less time in the hospital. For this reason, cord blood has been falling out of favor. Public banks have started scaling down their collections; the New York Blood Center, which had launched the world’s first public bank, recently stopped collecting new donations. How cord blood gets used in the future is still unknown.

    More than 30 years ago after Kurtzberg first treated Farrow, she is still in touch with him. He’s 39 now, and doing well. Having watched cord banking grow and evolve over the years, she remains a proponent of public banking and the possibilities ahead. When it comes to private banks, however, she says, “I don’t think it’s a necessity. I think it’s nice to have if you can do it.” There isn’t much harm in private banking, after all, as long as parents can afford the several thousand dollars over their child’s lifetime.

    Afford might be the key word here. The ads for cord-blood banking feel a lot like those for any number of “nice to have” baby products aimed at anxious parents, be they organic diapers or BPA-free wooden toys tailored to your child’s age and cognitive development. If anything, the stakes of cord-blood banking are higher than anything else you might choose to buy. The opportunity only comes around “once in a lifetime,” and it could literally save your child’s life—even if the chances of that are very, very small. “It’s playing to parental guilt and the desire for parents to have healthy children and do whatever they can for their kids,” says Timothy Caulfield, a health-law professor at the University of Alberta who has studied cord-blood banks. “There’s a huge market based on exactly that.”

    It’s telling, perhaps, that Cord Blood Registry ran a giveaway of $20,000 worth of baby products this summer. The curated package of luxury “baby essentials” resembled the registry of parents who want the best for their kid, and can afford it. Included were a Snoo smart bassinet ($1,695), an Uppababy stroller and car seat ($1,400), Coterie diapers ($100 for a month’s supply, guaranteed to be “free of fragrance, lotion, latex, rubber, dyes, alcohol, heavy metals, parabens, phthalates, chlorine bleaching, VOCs, and optical brighteners”), and, of course, a lifetime of cord-blood and tissue banking ($11,860).

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    Sarah Zhang

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  • Scientists Discover Protein Partners that Could Heal Heart Muscle

    Scientists Discover Protein Partners that Could Heal Heart Muscle

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    Newswise — CHAPEL HILL, N.C. – Scientists at the UNC School of Medicine have made a significant advance in the promising field of cellular reprogramming and organ regeneration, and the discovery could play a major role in future medicines to heal damaged hearts.

    In a study published in the journal Cell Stem Cell, scientists at the University of North Carolina at Chapel Hill discovered a more streamlined and efficient method for reprogramming scar tissue cells (fibroblasts) to become healthy heart muscle cells (cardiomyocytes). Fibroblasts produce the fibrous, stiff tissue that contributes to heart failure after a heart attack or because of heart disease. Turning fibroblasts into cardiomyocytes is being investigated as a potential future strategy for treating or even someday curing this common and deadly condition.

    Surprisingly, the key to the new cardiomyocyte-making technique turned out to be a gene activity-controlling protein called Ascl1, which is known to be a crucial protein involved in turning fibroblasts into neurons. Researchers had thought Ascl1 was neuron-specific.

    “It’s an outside-the-box finding, and we expect it to be useful in developing future cardiac therapies and potentially other kinds of therapeutic cellular reprogramming,” said study senior author Li Qian, PhD, associate professor in the UNC Department of Pathology and Lab Medicine and associate director of the McAllister Heart Institute at UNC School of Medicine.

    Scientists over the last 15 years have developed various techniques to reprogram adult cells to become stem cells, then to induce those stem cells to become adult cells of some other type. More recently, scientists have been finding ways to do this reprogramming more directly – straight from one mature cell type to another. The hope has been that when these methods are made maximally safe, effective, and efficient, doctors will be able to use a simple injection into patients to reprogram harm-causing cells into beneficial ones.

    “Reprogramming fibroblasts has long been one of the important goals in the field,” Qian said. “Fibroblast over-activity underlies many major diseases and conditions including heart failure, chronic obstructive pulmonary disease, liver disease, kidney disease, and the scar-like brain damage that occurs after strokes.”

    In the new study, Qian’s team, including co-first-authors Haofei Wang, PhD, a postdoctoral researcher, and MD/PhD student Benjamin Keepers, used three existing techniques to reprogram mouse fibroblasts into cardiomyocytes, liver cells, and neurons. Their aim was to catalogue and compare the changes in cells’ gene activity patterns and gene-activity regulation factors during these three distinct reprogrammings.

    Unexpectedly, the researchers found that the reprogramming of fibroblasts into neurons activated a set of cardiomyocyte genes. Soon they determined that this activation was due to Ascl1, one of the master-programmer “transcription factor” proteins that had been used to make the neurons.

    Since Ascl1 activated cardiomyocyte genes, the researchers added it to the three-transcription-factor cocktail they had been using for making cardiomyocytes, to see what would happen. They were astonished to find that it dramatically increased the efficiency of reprogramming – the proportion of successfully reprogrammed cells – by more than ten times. In fact, they found that they could now dispense with two of the three factors from their original cocktail, retaining only Ascl1 and another transcription factor called Mef2c.

    In further experiments they found evidence that Ascl1 on its own activates both neuron and cardiomyocyte genes, but it shifts away from the pro-neuron role when accompanied by Mef2c. In synergy with Mef2c, Ascl1 switches on a broad set of cardiomyocyte genes.

    “Ascl1 and Mef2c work together to exert pro-cardiomyocyte effects that neither factor alone exerts, making for a potent reprogramming cocktail,” Qian said.

    The results show that the major transcription factors used in direct cellular reprogramming aren’t necessarily exclusive to one targeted cell type.

    Perhaps more importantly, they represent another step on the path towards future cell-reprogramming therapies for major disorders. Qian says that she and her team hope to make a two-in-one synthetic protein that contains the effective bits of both Ascl1 and Mef2c, and could be injected into failing hearts to mend them.

    “Cross-lineage Potential of Ascl1 Uncovered by Comparing Diverse Reprogramming Regulatomes” was co-authored by Haofei Wang, Benjamin Keepers, Yunzhe Qian, Yifang Xie, Marazzano Colon, Jiandong Liu, and Li Qian.

    Funding was provided by the American Heart Association and the National Institutes of Health (T32HL069768, F30HL154659, R35HL155656, R01HL139976, R01HL139880).

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    University of North Carolina School of Medicine

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  • Mouse Embryo Experiment Could Teach Us About Miscarriages

    Mouse Embryo Experiment Could Teach Us About Miscarriages

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    Oct. 3, 2022 — Miscarriages are a devastating, if natural, occurrence. Nearly 1 million pregnant people in the U.S. experience a miscarriage every year, according to the National Advocates for Pregnant Women. New research could lend insight into the causes of some types of early pregnancy loss and maybe one day help prevent miscarriages. 

    In the bioengineering breakthrough, scientists created a mouse embryo in a lab without using sperm or eggs. The experimental embryo, called a model, was grown out of stem cells and developed further than any earlier experiments, with a beating heart and the foundation of a brain within a yolk sac, according to the researchers. 

    The experiment, while conducted with mouse stem cells, could help explain why some human pregnancies fail. Miscarriages occur in up to 15% of pregnancies confirmed by doctors, according to some studies, and also for many pregnant people before they even knew of the pregnancy. This experiment gives researchers a glimpse of a critical developmental stage for the first time. 

    “We are building mouse embryo models, but they have exactly the same principle as real human embryos,” says lead researcher Magdalena Zernicka-Goetz, PhD, professor in mammalian development and stem cell biology at Cambridge University in the U.K. “That’s why they tell us about real pregnancy.”

    With the new mouse models, the researchers can study implantation, the stage when embryos embed themselves in the mother’s body – a stage that’s often difficult for embryos to survive. The same process happens in mouse embryos, which develop very similarly to human embryos at this early stage of life.

    Deciphering the Stem Cell Code 

    Six years ago, researchers from the University of Cambridge and the California Institute of Technology set out to create models that would allow them to study fetal development in three-dimensional form but without the need for human embryos. 

    “We are trying to understand the major principles of time and space that have to be fulfilled” to form a successful pregnancy, Zernicka-Goetz explains. “If those principles are not fulfilled, the pregnancies are terminated, even before women know they’re pregnant.” 

    There are limits on using human embryos for research, and previous experiments have tended to replicate only one aspect of development. That led to two-dimensional experiments: flat cells on the bottom of a petri dish that lack the structural organization of real tissue. 

    The new models are three-dimensional with beating hearts and the yolk sacs in which embryos feed and grow. The models even progressed to forming the beginning of a brain – a research first. 

    The scientists used the foundational cellular “building blocks” called stem cells and managed to get the cells to communicate along a timeline that mimicked natural development, simulating those developmental stages, says Zernicka-Goetz. Those “building blocks” are actually three types of stem cells: pluripotent stem cells that build body tissue, and two other types of stem cells that build the placenta and the amniotic sac. 

    Completing the experiment required the right quantity of each stem cell type. The researchers also needed to understand how those cells exchange information before they can begin to grow. The researchers were able to “decipher the code” of how the cells talk to each other, Zernicka-Goetz says.

    Initially, the three types of stem cells combine, almost like a soup, but when the timing is right, they have to recognize each other and sort themselves. Next, each stem cell type must start building a different structure necessary for fetal development. Zernicka-Goetz thinks of this construction as the architecture of human tissue. 

    With the new technique, researchers can continue investigating the implantation stage and beyond. And they did – tweaking the experiment to create a genetically flawed embryo on purpose.

    Goetz and her team eliminated a certain gene known to regulate how cells establish their own identities. Doing so resulted in the same brain development flaws as in human embryos, providing “a proof of concept” that the experimental models can be used to study other genetic mysteries, she says. 

    Scientists are still in the dark about what some genes do, as well as the point when they become critical to brain development. 

    “Many genes have very early roles in specifying, for example, the position of the head and also how our brain will function,” Zernicka-Goetz says. “We can now use this model system to assess the function of those genes.” 

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  • Leading UK Biotechnology Company Appoints Global Expert Transplant Surgeon and Research Lead as Chief Medical Officer

    Leading UK Biotechnology Company Appoints Global Expert Transplant Surgeon and Research Lead as Chief Medical Officer

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    Press Release
    –


    updated: Oct 17, 2017


    London, United Kingdom, October 17, 2017 (Newswire.com)
    –
    ​Precious Cells (International Ltd) welcomes Dr Kourosh Saeb-Parsy, Consultant Transplant Surgeon, University Lecturer and Regenerative Medicine Research Lead, as their new Chief Medical Officer.

    This newly created role is the latest in a series of expert senior management appointments at Precious Cells, as the team strive towards achieving their vision to transform the future of global health by connecting the 7 billion potential stem cell donors worldwide.  The team of seasoned international experts have come together to tackle the global challenges facing transplantation medicine by creating access to stem cell treatments that will allow effective, affordable personalised medicine to become a worldwide reality in our lifetime.

    Dr Husein Salem, CEO, Precious Cells explains:

    “One of our key goals is to establish a strong, experienced clinical leadership team for achieving the clinical strategy of the organisation’s vision and mission. I am delighted that Dr Saeb-Parsy has joined us. Not only bringing his global experience and reputation for quality and excellence in transplantation and regenerative medicine, but also strengthening our strategic alliance with Cambridge University.”

    Dr Saeb-Parsy says:

    “I am passionate about creating links and networks to connect researchers, clinicians and commercial organisations to realise the promise of regenerative medicine. I am delighted to join Precious Cells International and I looks forward to working with the whole team to deliver the vision of connecting 7 billion stem cell donors.”

    Dr Saeb-Parsy is a Lecturer at the Department of Surgery, University of Cambridge and a Consultant Transplant Surgeon at Cambridge University Hospitals NHS Trust (Addenbrooke’s Hospital). His clinical interests include adult kidney, pancreas and liver transplantations.

    He leads a translational research group in regenerative medicine. The focus of his multidisciplinary and collaborative research is the cryopreservation, function and immune response to cellular therapies, including haematopoietic stem cells.

    Additionally, Dr Saeb-Parsy is involved across a number of collaborative research projects that are underpinned by the use of donor human tissue, including the investigation of regenerative cellular therapies derived from stem cells for the treatment of diabetes and liver disease.

    This is perfectly aligned with the tremendous work that Precious Cells has been focusing on, including the creation of a full proprietary “vein-to-vein supply chain™” platform that enables the company to supply stem cells of the highest quality for transplants and research. Their platform uses advanced systems and processes to work with hematopoietic stem cells, mesenchymal stem cells and adult blood rare pluripotent stem cells to create the next generation of cell and gene therapy solutions. 

    Source: Precious Cells

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