ReportWire

Tag: Biotech

  • 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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  • 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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  • New sensor uses MRI to detect light deep in the brain

    New sensor uses MRI to detect light deep in the brain

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    Newswise — CAMBRIDGE, MA — Using a specialized MRI sensor, MIT researchers have shown that they can detect light deep within tissues such as the brain.

    Imaging light in deep tissues is extremely difficult because as light travels into tissue, much of it is either absorbed or scattered. The MIT team overcame that obstacle by designing a sensor that converts light into a magnetic signal that can be detected by MRI (magnetic resonance imaging).

    This type of sensor could be used to map light emitted by optical fibers implanted in the brain, such as the fibers used to stimulate neurons during optogenetic experiments. With further development, it could also prove useful for monitoring patients who receive light-based therapies for cancer, the researchers say.

    “We can image the distribution of light in tissue, and that’s important because people who use light to stimulate tissue or to measure from tissue often don’t quite know where the light is going, where they’re stimulating, or where the light is coming from. Our tool can be used to address those unknowns,” says Alan Jasanoff, an MIT professor of biological engineering, brain and cognitive sciences, and nuclear science and engineering.

    Jasanoff, who is also an associate investigator at MIT’s McGovern Institute for Brain Research, is the senior author of the study, which appears today in Nature Biomedical Engineering. Jacob Simon PhD ’21 and MIT postdoc Miriam Schwalm are the paper’s lead authors, and Johannes Morstein and Dirk Trauner of New York University are also authors of the paper.

    A light-sensitive probe

    Scientists have been using light to study living cells for hundreds of years, dating back to the late 1500s, when the light microscope was invented. This kind of microscopy allows researchers to peer inside cells and thin slices of tissue, but not deep inside an organism.

    “One of the persistent problems in using light, especially in the life sciences, is that it doesn’t do a very good job penetrating many materials,” Jasanoff says. “Biological materials absorb light and scatter light, and the combination of those things prevents us from using most types of optical imaging for anything that involves focusing in deep tissue.”

    To overcome that limitation, Jasanoff and his students decided to design a sensor that could transform light into a magnetic signal.

    “We wanted to create a magnetic sensor that responds to light locally, and therefore is not subject to absorbance or scattering. Then this light detector can be imaged using MRI,” he says.

    Jasanoff’s lab has previously developed MRI probes that can interact with a variety of molecules in the brain, including dopamine and calcium. When these probes bind to their targets, it affects the sensors’ magnetic interactions with the surrounding tissue, dimming or brightening the MRI signal.

    To make a light-sensitive MRI probe, the researchers decided to encase magnetic particles in a nanoparticle called a liposome. The liposomes used in this study are made from specialized light-sensitive lipids that Trauner had previously developed. When these lipids are exposed to a certain wavelength of light, the liposomes become more permeable to water, or “leaky.” This allows the magnetic particles inside to interact with water and generate a signal detectable by MRI.

    The particles, which the researchers called liposomal nanoparticle reporters (LisNR), can switch from permeable to impermeable depending on the type of light they’re exposed to. In this study, the researchers created particles that become leaky when exposed to ultraviolet light, and then become impermeable again when exposed to blue light. The researchers also showed that the particles could respond to other wavelengths of light.

    “This paper shows a novel sensor to enable photon detection with MRI through the brain. This illuminating work introduces a new avenue to bridge photon and proton-driven neuroimaging studies,” says Xin Yu, an assistant professor radiology at Harvard Medical School, who was not involved in the study.

    Mapping light

    The researchers tested the sensors in the brains of rats — specifically, in a part of the brain called the striatum, which is involved in planning movement and responding to reward. After injecting the particles throughout the striatum, the researchers were able to map the distribution of light from an optical fiber implanted nearby.

    The fiber they used is similar to those used for optogenetic stimulation, so this kind of sensing could be useful to researchers who perform optogenetic experiments in the brain, Jasanoff says.

    “We don’t expect that everybody doing optogenetics will use this for every experiment — it’s more something that you would do once in a while, to see whether a paradigm that you’re using is really producing the profile of light that you think it should be,” Jasanoff says.

    In the future, this type of sensor could also be useful for monitoring patients receiving treatments that involve light, such as photodynamic therapy, which uses light from a laser or LED to kill cancer cells.

    The researchers are now working on similar probes that could be used to detect light emitted by luciferases, a family of glowing proteins that are often used in biological experiments. These proteins can be used to reveal whether a particular gene is activated or not, but currently they can only be imaged in superficial tissue or cells grown in a lab dish.

    Jasanoff also hopes to use the strategy used for the LisNR sensor to design MRI probes that can detect stimuli other than light, such as neurochemicals or other molecules found in the brain.

    “We think that the principle that we use to construct these sensors is quite broad and can be used for other purposes too,” he says.

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    The research was funded by the National Institutes of Health, the G. Harold and Leyla Y. Mathers Foundation, a Friends of the McGovern Fellowship from the McGovern Institute for Brain Research, the MIT Neurobiological Engineering Training Program, and a Marie Curie Individual Fellowship from the European Commission.

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    Massachusetts Institute of Technology (MIT)

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  • Shrinking hydrogels enlarge nanofabrication options

    Shrinking hydrogels enlarge nanofabrication options

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    Newswise — Carnegie Mellon University’s Yongxin (Leon) Zhao and the Chinese University of Hong Kong’s Shih-Chi Chen have a big idea for manufacturing nanodevices.

    Zhao’s Biophotonics Lab develops novel techniques to study biological and pathological processes in cells and tissues. Through a process called expansion microscopy, the lab works to advance techniques to proportionally enlarge microscopic samples embedded in a hydrogel, allowing researchers to be able to view fine details without upgrading their microscopes.

    In 2019, an inspiring conversation with Shih-Chi Chen, who was visiting Carnegie Mellon as an invited speaker and is a professor at the Chinese University of Hong Kong’s Department of Mechanical and Automation Engineering, sparked a collaboration between the two researchers. They thought they could use their combined expertise to find novel solutions for the long-standing challenge in microfabrication: developing ways to reduce the size of printable nanodevices to as small as 10s of nanometers or several atoms thick.

    Their solution is the opposite of expansion microscopy: create the 3D pattern of a material in hydrogel and shrink it for nanoscale resolution.

    “Shih-Chi is known for inventing the ultrafast two-photon lithography system,” said Zhao, the Eberly Family Career Development Associate Professor of Biological Sciences. “We met during his visit to Carnegie Mellon and decided to combine our techniques and expertise to pursue this radical idea.”

    The results of the collaboration open new doors for designing sophisticated nanodevices and are published in the journal Science.

    While conventional 3D nanoscale printers focus a laser point to serially process materials and take a long time to complete a design, Chen’s invention changes the width of the laser’s pulse to form patterned light sheets, allowing for a whole image containing hundreds of thousands of pixels (voxels) to be printed at once without compromising the axial resolution.

    The manufacturing technique is called femtosecond project two-photon lithography, or FP-TPL. The method is up to 1,000 times faster than previous nanoprinting techniques and could lead to cost-effective large scale nanoprinting for use in in biotechnology, photonics or nanodevices.

    For the process, researchers would direct the femtosecond two-photon laser to modify the network structure and pore size of the hydrogel, which then creates boundaries for water-dispersible materials. The hydrogel would then be immersed in water containing nanoparticles of metal, alloys, diamond, molecular crystals, polymers or fountain pen ink.

    “Through fortuitous happenstance, the nanomaterials we tried were all attracted automatically to the printed pattern in hydrogel and assembled beautifully,” Zhao said. “As the gel shrinks and dehydrates, the materials become even more densely packed and connect to each other.”

    For example, if a printed hydrogel is placed into a silver nanoparticle solution, the silver nanoparticles self-assemble to the gel along the laser-printed pattern. As the gel dries out, it can shrink to up to 13 times its original size, making the silver dense enough to form a nano silver wire and conduct electricity, Zhao said.

    Because the gels are three-dimensional, printed patterns can be as well.

    As a demonstration of the technique’s use for encrypted optical storage — such as how CDs and DVDs are written and read with a laser — the team designed and built a seven-layer 3D nanostructure that read “SCIENCE” after it was optically decrypted.

    Each layer contained a 200×200-pixel hologram of a letter. After shrinking the sample the entire structure appears as a translucent rectangle under an optical microscope. One would need the right information on how much to expand the sample and where to shine a light through to read the information.

    “Based on our result, the technique can pack 5 petabits worth of information in a tiny cubic centimeter of space. That’s roughly 2.5 times of all U.S. academic research libraries combined.” he said.

    Zhao said that in the future the researchers’ goal is to build functional nanodevices with multiple materials.

    “In the end we would like to use the new technology to fabricate functional nanodevices, like nanocircuits, nanobiosensors, or even nanorobots for different applications,” Zhao said. “We are only limited by our imagination.”

    In addition to Zhao and Chen, co-authors on the Science paper, “3D Nanofabrication via Ultrafast Laser Patterning and Kinetically-regulated Material Assembly,” include Fei Han, Songyun Gu, Ni Zhao, all of the Chinese University of Hong Kong and Aleks Klimas, of Carnegie Mellon.

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    Carnegie Mellon University

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  • Ultrafast and ultra-sensitive protein detection method allows for ultra-early disease diagnoses

    Ultrafast and ultra-sensitive protein detection method allows for ultra-early disease diagnoses

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    Newswise — Osaka, Japan – Protein detection based on antigen–antibody reaction is vital in early diagnosis of a wide range of diseases. How to effectively detect proteins, however, has frequently bedeviled researchers. Osaka Metropolitan University scientists have discovered a new principle underlying light-induced acceleration of antigen–antibody reaction, allowing for simple, ultrafast, and highly sensitive detection of proteins. Their findings were published in Communications Biology.

    “The antigen–antibody reaction is a biochemical reaction that plays a crucial role in immunity, the body’s defense function,” explained lead researcher Professor Takuya Iida, Director of the Research Institute for Light-induced Acceleration System at Osaka Metropolitan University. Methods to analyze trace amounts of proteins based on antigen–antibody reaction enable diagnosis at an early stage of many diseases, including cancer, dementia, and microbial infections. However, such methods either have limited sensitivity or require complex and time-consuming processing to allow antigen–antibody reactions to occur.

    Aiming to accelerate antigen–antibody reactions, the researchers introduced target proteins and probe particles, with modified antibodies that selectively bind to the target proteins, into a channel that is as narrow as a human hair or artery and then applied irradiation with infrared laser light for 3 minutes, making it possible to carry out detection at a sensitivity approximately 100 times higher than that of conventional protein testing.

    The researchers achieved, for the first time, the rapid measurement of trace amounts of target proteins on the order of tens of attograms (ag = 10−18 g; one quintillionth of a gram) after only 3 minutes of laser irradiation.

    The study results demonstrate that rapid and highly sensitive detection can be achieved by condensing proteins through the simple operation of confining them in a small space and irradiating them with a laser to accelerate the reaction. These findings will facilitate the detection of disease-related substances from a small amount of body fluids, such as a single drop of blood, and will assist in the discovery of novel disease markers, potentially leading to breakthroughs in the development of systems for ultra-early diagnosis of various diseases.

    “In an interdisciplinary collaboration beyond physics, chemistry, and biology, we uncovered a new principle underlying the control of antigen–antibody reaction by optical force, or light-induced force,” concluded Professor Iida. “I hope that the advantage of being able to measure trace markers with high sensitivity and speed by simple laser irradiation will aid in ultra-early diagnosis.”

     

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    About OMU

    Osaka Metropolitan University is a new public university established by a merger between Osaka City University and Osaka Prefecture University in April 2022. For more science news, see https://www.omu.ac.jp/en/info/research-news/, and follow @OsakaMetUniv_en, or search #OMUScience.

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    Osaka City University

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  • CRISPR Technology Improves Huntington’s Disease Symptoms in Models

    CRISPR Technology Improves Huntington’s Disease Symptoms in Models

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    Newswise — Huntington’s disease (HD) is a neurological disorder that causes progressive loss of movement, coordination and cognitive function. It is caused by a mutation in a single gene called huntingtin or HTT. More than 200,000 people worldwide live with the genetic condition, approximately 30,000 in the United States. More than a quarter of a million Americans are at risk of inheriting HD from an affected parent. There is no cure.

    But in a new study, published December 12, 2022 in Nature Neuroscience, researchers at University of California San Diego School of Medicine, with colleagues elsewhere, describe using RNA-targeting CRISPR/Cas13d technology to develop a new therapeutic strategy that specifically eliminates toxic RNA that causes HD.

    CRISPR is known as a genome-editing tool that allows scientists to add, remove or alter genetic material at specific locations in the genome. It is based on a naturally occurring immune-defense system used by bacteria. However, current strategies run the risk of off-target edits at unintended sites that may cause permanent and inheritable chromosomal insertions or genome alterations. Because of this, significant efforts have focused on identifying CRISPR systems that target RNA directly without altering the genome.

    In the case of HD, the condition is caused by repetitive and damaging sequences in the HTT gene.

    Our cells have a hard time copying repetitive DNA, and these copying errors can cause repetitive sequences to grow longer with each generation,” said senior study author Gene Yeo, PhD, professor of cellular and molecular medicine at UC San Diego School of Medicine.

    “In the Huntingtin gene, these repeats can sometimes grow to many times their normal length, with the resulting repeat-expanded protein tending to aggregate and form toxic clumps in a part of the brain called the striatum that is important for regulating movement. The loss of functional neurons in the striatum ultimately leads to HD symptoms.”

    With colleagues at UC Irvine and Johns Hopkins University, Yeo and his team investigated whether recently described RNA-targeting CRISPR technology could be used to affect RNA (a chemical intermediate between DNA instructions and protein production) accumulation associated with HD.

    They used viral vehicles to deliver the therapy to neuronal cultures, which were developed from stem cells derived from patients with HD, and found that the approach not only targeted and destroyed mutant RNA molecules, but also cleared out toxic protein buildup. They also demonstrated that expression of other human genes was generally not disrupted by the therapy.

    “Our goal was to engineer a type of therapy that would only target the toxic RNA that causes HD and could keep the rest of the human genome and transcriptome intact,” said co-first author Kathryn Morelli, PhD, a research fellow in Yeo’s lab. “We specifically screened our top therapeutic constructs in HD patient cell lines to make sure of it.”

    Development of effective therapies for HD has proven challenging. In 2021, for example, two clinical trials for promising gene therapies were halted following disappointing results performance. Both potential drugs had been touted as game-changers for HD. Currently, no treatments can alter the course of the disease, though medications can lessen some symptoms.

    “The Huntington’s community was devastated when the clinical trials failed, primarily due to target specificity and toxic effects,” said Yeo. “But their termination has only re-energized the scientific community to find alternative strategies.”

    Yeo’s lab collaborated with Wenzhen Duan, MD, PhD, professor of psychiatry and behavioral sciences, at Johns Hopkins Medicine to conduct preclinical testing in mice. Duan, with co-first author Qian Wu, PhD, found that the therapy improved motor coordination, attenuated striatal degradation and reduced toxic protein levels in a mouse model of HD. The improvements lasted for at least 8 months without adverse effects and minimal off-target effects on other RNA molecules.

    Co-authors include: Maya L. Gosztyla, Ryan J. Marina, Kari Lee, Krysten L. Jones, Megan Huang and Allison Li, all at UC San Diego; Hongshuai Liu, Minmin Yao and Chuangchuang Zhang, Johns Hopkins University; Jiaxu Chen, Beijing University of Chinese Medicine; and Charlene Smith-Geater and Leslie M. Thompson, UC Irvine.

    Funding for this research came, in part, from the National Institutes of Health (grants EY029166, NS103172,MH107367, AI132122, HG004659, HG009889, NS099397, NS124084, T32GM008666 ) the Bev Hartig Huntington’s Disease Foundation, an NIH NS112654-03 postdoctoral fellowship, a University of California President’s Postdoctoral Fellowship, the Paul G. Allen Foundation, the China Scholarship Council and the National Natural Science Foundation of China (82174278 and 81973748), the Hereditary Disease Foundation, an NIH predoctoral fellowship (NS111859), a National Science Foundation Graduate Research Fellowship (DGE-2038238),a Myotonic Dystrophy Foundation Doctoral Research Fellowship, an Association for Women in Science Scholarship and a Triton Research and an Experiential Learning Scholarship from Eureka! Research Scholarship.

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    Disclosures: Gene Yeo is a scientific advisory board member of Jumpcode Genomics and a co-founder, member of the Board of Directors, scientific advisory board member, equity holder and paid consultant for Locanabio and Eclipse BioInnovations. He is also a Distinguished Visiting Professor at the National University of Singapore.

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    University of California San Diego

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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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  • Science misinformation on GMOs reaches quarter of a billion people, study finds

    Science misinformation on GMOs reaches quarter of a billion people, study finds

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    Newswise — 17 NOVEMBER 2022, ITHACA, NEW YORK: Science misinformation about genetically modified crops and foods had a potential global readership of over a quarter of a billion people, according to a new study published by the Alliance for Science, which combats anti-science misinformation on topics like climate, vaccines and GMOs.

    The study assessed top English-language media from around the world, with stories published over a two-year period between January 2019 and January 2021. Articles were assessed for misinformation, defined as statements that disagreed with the scientific consensus on the safety of genetic engineering.

    Overall, 9% (47) of the 535 relevant articles containing ‘GMO’-related keywords contained misinformation. This false information was considered likely to have had a potential reach of 256 million people.

    The problem is particularly acute in Africa, where one-fifth of media coverage of genetically modified foods contained misinformation. The corresponding figures for North America and Europe were 5% and 7%, respectively.

    As well as regional tags, the articles were also subjected to sentiment analysis. While an overwhelming majority of articles were categorized as ‘neutral,’ the majority of misinformation was rated as ‘negative’ in tone. There were no articles containing misinformation with a positive tone towards GMOs.

    The biggest category of misinformation concerned human health. This category includes articles containing claims that GMOs cause cancer or other health impacts without refutation, because such claims contradict a worldwide scientific consensus that food from genetically engineered crops is as safe as food from non-genetically engineered crops. Misinformation on GMOs and human health also had the highest readership, achieving a potential reach of 139 million people.

    The study was conducted in partnership with Cision Media, using its NextGen database of global media. Sentiment analysis and categorization was performed manually, not by machine.

    The paper, which is published in the peer-reviewed journal GM Crops & Food, is titled “Misinformation in the media: global coverage of GMOs 2019-2021.” The lead author is Mark Lynas, climate and research lead at the Alliance for Science, which is based at the Boyce Thompson Institute in Ithaca, New York.

    Lynas has previously published work with the Alliance for Science quantifying the scientific consensus on climate change, and examining media misinformation both on COVID-19 and vaccines. This new paper is thought to be the first to quantify the extent of GMO-related misinformation in the world’s media based on a comprehensive dataset.

    On the issue of GMO misinformation, Lynas said: “Our results show that misinformation about GMOs is still a huge problem, and that hundreds of millions of people are being given false information that contradicts the scientific consensus on the safety of genetic engineering. Make no mistake: misinformation about GMOs can be as harmful to society as misinformation on vaccines or climate change. The media must do better, and stop publishing false claims on this subject spread by anti-science activists.”

    Dr Sheila Ochugboju, executive director the Alliance for Science, added: “What is most worrying is that the problem of misinformation on GMOs is particularly acute in Africa, where it is harming the livelihoods of smallholder farmers by preventing them from accessing new crop varieties that are resistant to pests and to drought caused by climate change.”

    She added: “It is vital that the benefits of scientific innovation are not denied to people in the Global South,” and vowed that the Alliance for Science will continue to combat misinformation on this subject and others via its Nairobi-based Global South Hub, and by working with partners including the Open Forum for Agricultural Biotechnology in Africa (OFAB).

    About Boyce Thompson Institute:

    Opened in 1924, Boyce Thompson Institute is a premier life sciences research institution located in Ithaca, New York. BTI scientists conduct investigations into fundamental plant and life sciences research with the goals of increasing food security, improving environmental sustainability in agriculture, and making basic discoveries that will enhance human health. Throughout this work, BTI is committed to inspiring and educating students and to providing advanced training for the next generation of scientists. BTI is an independent nonprofit research institute that is also affiliated with Cornell University. For more information, please visit BTIscience.org.

    ###

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    Boyce Thompson Institute

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  • Personalising whole genome sequencing doubles diagnosis of rare diseases

    Personalising whole genome sequencing doubles diagnosis of rare diseases

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    Newswise — Tailoring the analysis of whole genome sequencing to individual patients could double the diagnostic rates of rare diseases, finds a new study led by UCL researchers.

    In 2018, the UK’s department of health announced an NHS Genomic Medicine Service, which allows patients with rare diseases to have their entire genetic code read in the hope of providing a much-needed diagnosis.

    However, the interpretation of this data can be extremely challenging and many people with complex, rare genetic diseases still do not receive a molecular answer to the cause of their problems.

    In the study, published in Nature Communications, researchers at The London Mitochondrial Centre at UCL Queen Square Institute of Neurology and UCL Great Ormond Street Institute of Child Health sought to offer such patients an improved chance of receiving a genetic diagnosis.

    To do so, they tested how using a genomic medicine team of specialist doctors, bioinformaticians, and scientists could boost the capabilities of NHS diagnostic laboratories beyond the standard semi-automated analysis of data. The UCL team re-evaluated undiagnosed cases to identify clues that might help direct further, more personalised analysis. They subsequently applied additional bioinformatic approaches, using advanced computer technologies to identify genetic alterations in a patients’ DNA which may be causing disease but had been overlooked during routine testing.

    The work included 102 undiagnosed patients, suspected of having a primary mitochondrial disease (a large group of incurable genetic disorders that affect children and adults, associated with a broad spectrum of medical problems, severe disabilities, and reduced lifespan), who had undergone whole genome sequencing via the NHS’s 100,000 Genomes Project.

    This personalised approach increased the diagnostic rate from 16.7% to 31.4%. It also detected potential disease-causing variants in a further 3.9% of patients.

    Lead author, Dr Robert Pitceathly (co-lead for the London NHS Highly Specialised Service for Rare Mitochondrial Disorders and a research group leader at UCL Queen Square Institute of Neurology), said: “The NHS has invested heavily in advanced genetic technologies. Consequently, the UK has established itself at the forefront of diagnostic whole genome sequencing. That said, some people with rare genetic diseases remain without a molecular diagnosis after their genome is analysed.

    “We believe investing in specialist genomic medicine teams is crucial, ensuring equitable access to dedicated multidisciplinary expertise and maximising diagnoses. On average, patients in our study waited over 30 years for a diagnosis – we now have the capability to solve such cases but need adequate workforce planning to support NHS diagnostic genetic laboratories in achieving this goal.”

    Receiving a genetic diagnosis is important as it allows patients to receive access to family planning, specialised IVF, and drugs trials. It can also permit targeted screening of known disease complications and access to drug studies.

    Dr Pitceathly said: “In this study, every new genetic diagnosis had a direct impact on patient care. This included additional check-ups for heart problems, hearing loss, and diabetes, and access to clinical trials.”

    Professor Michael Hanna, Director of UCL Queen Square Institute of Neurology said: “This work is a significant step forward in developing the best ways to maximise the benefits of genome analysis for patients. It clearly demonstrates that by combining automated approaches to genome analysis with data interpretation by a skilled multidisciplinary team the diagnostic rates doubles. This is an important finding that will influence how genomic medicine diagnostic services should evolve world-wide.”

    Co-author, Dr James Davison (Metabolic Medicine Department at Great Ormond Street Hospital and chair of the British Inherited Metabolic Diseases Group), said: “The journey to reaching a diagnosis for children and adults with rare, complex, medical conditions can be a very long process, and genomic medicine provides a transformative and powerful tool in helping reach that goal.

    “This study highlights the importance of the collaboration between specialist clinicians and genetic scientists in interpreting the results of genome sequencing to maximise the opportunity of reaching a diagnosis which can then help guide medical management and treatment options.”

    The researchers involved in this study are funded by the Medical Research Council.

    Patient story

    Rachel North was one of the patients involved in the trial and described getting a diagnosis as “life changing”. It has since allowed her to be screened for disease complications such as osteopenia, and these have been treated.

    She said: “I had attended so many hospitals over the past 20 years and had been searching so long, I never thought I’d get a diagnosis.

    “Wondering about it took up so much energy, and I was worried about my 12-year-old son, and if my condition would affect him. So, getting a rare recessive diagnosis was a relief and takes away fear of the unknown.

    “Having a diagnosis allows me to research my condition and be very proactive in managing it.

    “Anything that helps me understand and make sense of what is happening to my body helps me come to terms with it and gives me confidence that I am managing it as well as possible.”

    Notes to Editors

     

    William L. Macken, Micol Falabella, Caroline McKittrick, Chiara Pizzamiglio, Rebecca Ellmers, Kelly Eggleton, Cathy E. Woodward, Yogan Patel, Robyn Labrum, Genomics England Research Consortium, Rahul Phadke, Mary M. Reilly, Catherine DeVile, Anna Sarkozy, Emma Footitt, James Davison, Shamima Rahman, Henry Houlden, Enrico Bugiardini, Rosaline Quinlivan, Michael G. Hanna, Jana Vandrovcova, Robert D. S. Pitceathly. Specialist multidisciplinary input maximises rare disease diagnoses from whole genome sequencing, will be published in Nature Communications, on 7th November 2022 at 10:00 GMT / 05:00 ET.

     

    The DOI for this paper will be: 10.1038/s41467-022-32908-7

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    University College London

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  • Patient-Specific Cancer Tumours Replicated in 3D Bioprinting Advance

    Patient-Specific Cancer Tumours Replicated in 3D Bioprinting Advance

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    Externally peer reviewed: Yes

    Evidence type: Experimental study

    Subjects: Cells

     

    Newswise — Bowel cancer patients could in future benefit from a new 3D bioprinting technology which would use their own cells to replicate the complex cellular environment of solid tumours in 3D models. The University of Bristol-led advance, published in Biofabrication, would allow clinicians to treat the models, known as spheroids, with chemotherapy drugs and radiation to help them understand an individual patient’s resistance to therapies.

    Bowel cancer is the third-most prevalent cancer worldwide, a major cause of cancer-related deaths and is becoming more prevalent globally each year. While current therapies aim to shrink tumours through a combination of surgery, chemotherapy and/or radiotherapy, the heterogenous nature of bowel tumours mean that chemotherapy drugs have variable effects between patients. 

    In this new study, researchers developed a new 3D bioprinting platform with high content light microscopy imaging and processing. Using a mixture of bioinks and colorectal cancer cells, the team show they were able to replicate tumours in 3D spheroids.

    To investigate how the tumours might respond to drugs, dose-response profiles were generated from the spheroids which had been treated separately with chemotherapy drugs oxaliplatin (OX), fluorouracil (5FU), and radiotherapy. The spheroids were then imaged over time. Results from their experiment showed oxaliplatin was significantly less effective against tumour spheroids than in current 2D monolayer culture structures, when compared to fluorouracil.

    Professor Adam Perriman, Professor of Bioengineering from Bristol’s School of Cellular and Molecular Medicine, and founder of the cell therapy company CytoSeek, and the study’s lead author, explains the technology’s significance: “Clinically predictive models which allow clinicians to identify how well tumours respond to drugs before they are administered in patients, are still an unmet need. Two dimensional (2D) cell monolayer culture remains the standard for modelling in vitro drug effectiveness and safety. However, its poor in vivo predictive capability inhibits its use as a tool for drug discovery, drug repositioning and personalised medicine.

    “We have developed a high-throughput bioprinted bowel cancer spheroid platform with high levels of automation, information content, and low cell number requirement that mimics the 3D characteristics of tumours, and show that some tumours are more resistant to chemotherapy.

    “We anticipate that this new platform technology could have significant impact in human disease modelling for evaluation of oncology drug-response in 3D. This is a big step towards personalised medicine and helping to understand why certain patients respond to chemotherapy.”

    The study was supported by grants from the UKRI Future Leaders Fellowship, the EPSRC and the BBSRC Centre for Doctoral Training in Synthetic Biology.

    Paper

    A rapid high throughput bioprinted colorectal cancer spheroid platform for in vitro drug- and radiation-response by Adam W. Perriman et al. in Biofabrication.

    Ends

    Notes to editors

    Image available to download

    https://fluff.bris.ac.uk/fluff/u2/ficmc/co3MHXxxn_reIM5Lx2lUhA9MO/

    Caption: Electron micrograph of a grown, hydrogel-embedded tumour spheroid.

    Credit: University of Bristol

    Issued by the University of Bristol, UK.

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    University of Bristol

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  • DNA ‘Nanotransporters’ to treat cancer

    DNA ‘Nanotransporters’ to treat cancer

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    Newswise — A team of Canadian researchers from Université de Montréal has designed and validated a new class of drug transporters made of DNA that are 20,000 times smaller than a human hair and that could improve how cancers and other diseases are treated

    Reported in a new study in Nature Communications, these molecular transporters can be chemically programmed to deliver optimal concentration of drugs, making them more efficient than current methods.

    Optimal dosing at all times: a medical challenge

    One of the key ways to successfully treat disease is to provide and maintain a therapeutic drug dosage throughout treatment. Sub-optimal therapeutic exposure reduces efficiency and typically leads to drug resistance, while overexposure increases side effects.

    Maintaining an optimal concentration of drugs in the blood remains a major challenge in modern medicine. Since most drugs undergo rapid degradation, patients are forced to (and often forget) to take multiple doses at regular intervals. And because each patient has a distinct pharmacokinetic profile, the drugs concentration in their blood varies significantly.

    Observing that only about 50 per cent of cancer patients get an optimal drug dosage during certain chemotherapy, UdeM Chemistry associate professor Alexis Vallée-Bélisle, an expert in bio-inspired nanotechnologies, started to explore how biological systems control and maintain the concentration of biomolecules.

    “We have found that living organisms employ protein transporters that are programmed to maintain precise concentration of key molecules such as thyroid hormones, and that the strength of the interaction between these transporters and their molecules dictates the precise concentration of the free molecule,” he said.

    This simple idea led Valléé-Belisle – who holds a Canada Research Chair in bioengineering and bionanotechnology – and his research team to start developing artificial drug transporters that mimic the natural effect of maintaining a precise concentration of a drug during treatment.

    UdeM PhD student Arnaud Desrosiers, the first author of the study, initially identified and developed two DNA transporters: one for quinine, an antimalarial, and the other for doxorubicin, a commonly used drug for treating breast cancer and leukemia.

    He then demonstrated that these artificial transporters could be readily programmed to deliver and maintain any specific concentration of drug.

    “More interestingly, we also found that these nanotransporters could also be employed as a drug reservoir to prolong the effect of the drug and minimize its dosage during treatment,” said  Desrosiers.

    “Another impressive feature of these nanotransporters,” he added, “is that they can be directed to specific parts of the body where the drug is most needed – and that, in principle, should reduce most side effects.”

    Nanotreated mice: reduced cardiotoxicity

    To demonstrate the effectiveness of these nanotransporters, the researchers teamed up with Jeanne Leblond-Chain, a pharmacist at Université de Bordeaux, in France; Luc DesGroseillers, a biochemist at UdeM; Jérémie Berdugo, a pathologist at UdeM; Céline Fiset, a pharmacist at the Montreal Heart Institute; and Vincent De Guire, a clinical biochemist at the UdeM-affiliated Maisonneuve-Rosemont Hospital.

    Using the new drug transporter developed for doxorubicin, the team demonstrated that a specific drug-transporter formulation allows doxorubicin to be maintained in the blood and drastically reduces its diffusion towards key organs such as the heart, lungs and pancreas.

    In mice treated with this formulation, doxorubicin was maintained 18 times longer in the blood and cardiotoxicity was reduced as well, keeping the mice more healthy as evidenced by their normal weight gain. 

    “Another great property of our nanotransporters is their high versatility,” said Vallée-Bélisle.

    “For now, we have demonstrated the working principle of these nanotransporters for two different drugs. But thanks to the high programmability of DNA and protein chemistries, one can now design these transporters to precisely deliver a wide range of threrapeutic molecules.”

    And, he added, “additionally, these transporters could also be combined with human-designed liposomic transporters that are now being employed to deliver drugs at various rates.”

    A clinical study for blood cancers?

    The researchers are now eager to validate the clinical efficiency of their discovery. Since their doxorubicin nanotransporter is programmed to optimally maintain the drug in blood circulation, it could be deal to treat blood cancers, they believe.

    “We envision that similar nanotransporters may also be developed to deliver drugs to other specific locations in the body and maximize the presence of the drug at tumor sites,” said Vallée-Bélisle. “This would drastically improve the efficiency of drugs as well as decrease their side effects.”

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    Universite de Montreal

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  • Gene Therapy Rapidly Improves Night Vision in Adults with Congenital Blindness

    Gene Therapy Rapidly Improves Night Vision in Adults with Congenital Blindness

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    Newswise — PHILADELPHIA—Adults with a genetic form of childhood-onset blindness experienced striking recoveries of night vision within days of receiving an experimental gene therapy, according to researchers at the Scheie Eye Institute in the Perelman School of Medicine at the University of Pennsylvania.

    The patients had Leber Congenital Amaurosis (LCA), a congenital blindness caused by mutations in the gene GUCY2D. The researchers, whose findings are reported in the journal iScience, delivered AAV gene therapy, which carries the DNA of the healthy version of the gene, into the retina of one eye for each of the patients in accordance with the clinical trial protocol. Within days of being treated, each patient showed large increases, in the treated eye, of visual functions mediated by rod-type photoreceptor cells. Rod cells are extremely sensitive to light and account for most of the human capacity for low-light vision.

    “These exciting results demonstrate that the basic molecular machinery of phototransduction remains largely intact in some cases of LCA, and thus can be amenable to gene therapy even after decades of blindness,” said study lead author Samuel G. Jacobson, MD, PhD, a professor of Ophthalmology at Penn.

    LCA is one of the most common congenital blindness conditions, affecting roughly one in 40,000 newborns. The degree of vision loss can vary from one LCA patient to another but all such patients have severe visual disability from the earliest months of life. There are more than two dozen genes whose dysfunction can cause LCA.

    Up to 20 percent of LCA cases are caused by mutations in GUCY2D, a gene that encodes a key protein needed in retinal photoreceptor cells for the “phototransduction cascade”—the process that converts light to neuronal signals. Prior imaging studies have shown that patients with this form of LCA tend to have relatively preserved photoreceptor cells, especially in rod-rich areas, hinting that rod-based phototransduction could work again if functional GUCY2D were present. Early results with low doses of the gene therapy, reported last year, were consistent with this idea.

    The researchers used higher doses of the gene therapy in two patients, a 19- year-old man and a 32-year-old woman, who had particularly severe rod-based visual deficits. In daylight, the patients had some, albeit greatly impaired, visual function, but at night they were effectively blind, with light sensitivity on the order of 10,000 to 100,000 times less than normal.

    The researchers administered the therapy to just one eye in each patient, so the treated eye could be compared to the untreated eye to gauge treatment effects. The retinal surgery was performed by Allen C. Ho, MD, a professor of Ophthalmology at Thomas Jefferson University and Wills Eye Hospital. Tests revealed that, in both patients, the treated eyes became thousands of times more light-sensitive in low-light conditions, substantially correcting the original visual deficits. The researchers used, in all, nine complementary methods to measure the patients’ light sensitivity and functional vision. These included a test of room navigation skills in low-light conditions and a test of involuntary pupil responses to light. The tests consistently showed major improvements in rod-based, low-light vision, and the patients also noted functional improvements in their everyday lives, such as “can [now] make out objects and people in the dark.”

    “Just as striking was the rapidity of the improvement following therapy. Within eight days, both patients were already showing measurable efficacy,” said study co-author Artur V. Cideciyan, PhD, a research professor of Ophthalmology at Penn.

    To the researchers, the results confirm that GUCY2D gene therapy to restores rod-based photoreceptor functions—and suggest that GUCY2D–LCA patients with more severe rod-based dysfunction are likely to benefit most dramatically from the therapy. The practical message is that there should be an emphasis on rod vision measurements at screening of LCA candidates and in monitoring them throughout a treatment trial.

    The findings, the researchers said, also underscore the remarkable fact that in some patients with severe congenital vision loss, the retinal cell networks that mediate vision remain largely alive and intact, and need only the resupply of a missing protein to start working again, more or less immediately.

    The ongoing clinical trial is registered at clinicaltrials.gov as trial NCT03920007.

    Support for the research was provided by Atsena Therapeutics, Inc., the developer of the GUCY2D gene therapy; the National Institutes of Health (R01 EY11522); and by a CURE Formula grant from the Pennsylvania Department of Health.

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    Perelman School of Medicine at the University of Pennsylvania

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  • Study: Novel Imaging Technique Reveals Excellent Biologic Fixation in Cementless Knee Replacement

    Study: Novel Imaging Technique Reveals Excellent Biologic Fixation in Cementless Knee Replacement

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    Newswise — Cementless knee replacement, an alternative approach to the traditional surgery in which bone cement is used, is gaining interest among orthopedic surgeons. Using a novel MRI technique, researchers at Hospital for Special Surgery (HSS) found that a cementless implant demonstrated excellent biologic fixation, and even improved fixation of implant components in some areas in the joint, compared to the standard cemented implant.

    HSS hip and knee surgeon Geoffrey Westrich, MD, and colleagues in the HSS Radiology Department used an advanced imaging technique known as “multi-acquisition variable-resonance image combination selective MRI” to assess fixation in patients who had a cementless knee replacement compared to those whose implant was affixed with bone cement.

    “The purpose of our study was to quantify and compare the fixation of uncemented versus cemented knee replacement components,” said Dr. Westrich, lead investigator. “At an average patient follow-up of 16 months, our study demonstrated robust fixation of the cementless knee replacement components, with results comparable to the cemented total knee replacements. And while there was no clinically significant difference regarding overall fixation in the knee, there were some component areas in which cementless fixation appeared to be superior.” The study was published in the October edition of the journal Arthroplasty Today.  

    The HSS researchers performed MRIs in 20 patients who had a cementless knee replacement. A matched control group of 20 patients with a cemented knee replacement was also evaluated. The images were reviewed by a fellowship-trained musculoskeletal radiologist specializing in the interpretation of joint replacement MRI, including more than 20 years of experience in assessing bony fixation of knee replacement components.

    In a traditional knee replacement, implant components are secured in the joint using bone cement. It’s a tried-and-true technique that has worked well for decades. But eventually, over time, the cement may start to loosen from the bone and/or the implant. This loosening is the leading cause of revision surgery, in which a patient needs a second knee replacement.

    “With the cementless prosthesis, the components are press fit into place for biologic fixation, which basically means that the bone will grow into the implant,” explains Dr. Westrich, who believes a well-designed cementless implant will make loosening over time less likely. This could enable a total knee replacement to last much longer, a particular concern for younger patients.

    “Overall, traditional knee replacement offers excellent outcomes and longevity,” he says. “However, younger patients generally put more demands on their joint, causing more wear and tear and potential loosening. The cemented knee implant used in a traditional joint replacement usually lasts 15 to 20 years.”

    Cementless implants have been used successfully in total hip replacement surgery for many years. It has been much more challenging to develop a cementless prosthesis that would work well in the knee because of its particular anatomy, Dr. Westrich explains.

    “Early generation cementless implants had numerous design flaws resulting in loosening and poor survivorship compared to cemented knee replacements,” he says. “More contemporary cementless knee components such as those used in our study utilize highly porous surfaces to promote biologic fixation of the prosthesis. This should improve outcomes.”

    Candidates for the cementless procedure are generally patients under age 70 with good bone quality to promote biologic fixation. In addition to younger patients, Dr. Westrich notes that the cementless implant may prove to be a good option for very overweight patients who tend to put more stress on their joint replacement.

    “While our study found that early fixation of cementless total knee components are comparable, if not superior, to cemented total knee replacement, further study with a larger number of patients over a lengthier time period is needed to assess long-term durability and fixation.”

    Disclosure: Research support received from Stryker Corporation. 

     

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    Geoffrey Westrich, MD

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  • A New T-Cell activation assay based on Hyris qPCR Technology marks a disruptive approach for the detection of SARS-CoV-2 specific cellular immunity

    A New T-Cell activation assay based on Hyris qPCR Technology marks a disruptive approach for the detection of SARS-CoV-2 specific cellular immunity

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    A scientific paper recently published in Nature Biotechnology reveals new research regarding how we track and monitor T-cell patients’ immunity to SARS-CoV-2, leveraging the unique characteristics of Hyris System™. The study results from a joint effort of an international research team from the Icahn School of Medicine at Mount Sinai, Singapore Duke-NUS Medical School, laboratory diagnostic service providers Synlab, and Hyris.

    Press Release
    –

    Jun 15, 2022


    LONDON, June 15, 2022 (Newswire.com)
    –
    With over 460 million global cases thus far, 6 million of which have resulted in death, the COVID-19 pandemic from SARS-CoV-2 proved to be a dire health crisis on a global scale. In this concerning scenario, the unprecedented effort by the international scientific community is even more remarkable and led – in record time – to the deployment of mRNA and viral vector-based vaccines. With more than 10 billion total vaccine doses administered worldwide, vaccination campaigns have already started to attenuate this global crisis. In order to maximize vaccine effectiveness, the efficacy and duration of protective immunity will need to be systematically assessed and monitored as widely as possible.

    A team of internationally renowned medical scientists recently published a related paper in Nature Biotechnology, addressing the efficacy and sensitivity of a new type of assay to detect SARS-CoV-2 cellular immunity.

    “To date, antibody tests have been the typical, if not the only clinical endpoints commonly used to measure the immune response to SARS-CoV-2,” explains Antonio Bertoletti, Professor at Duke-NUS Medical School. “Both the humoral (antibodies) and cellular immune response act in coordination to achieve long-term protection from viral infections. Antibodies are important for preventing infection, protecting the body from disease, while cellular immunity is essential to eliminate virus-infected cells, thus helping to fight the disease itself,” concludes Professor Bertoletti. 

    Therefore, according to the study, measuring the T-cells’ response is a new disruptive approach to fighting SARS-CoV-2. An individual negative to an antibody test could still be protected thanks to responsive T-cells.

    This new study thus shows the relevance of a quantitative PCR approach to T-cell testing, thanks to the joint effort with SYNLAB, one of the world’s leading providers of laboratory diagnostic services, and Hyris, a global biotech company focused on AI-powered genetic analysis.

    The research leveraged Hyris’ signature technology, the disruptive Hyris System™.

    “These highly scalable screening methods will be particularly important, to monitor the magnitude and duration of functional cellular immunity towards emerging variants, thus helping to prioritize revaccination strategies in vulnerable populations,” states Cristina Lapucci, Head of Genetics and Molecular Biology at SYNLAB Italy.

    “We have been very committed to putting our System at such prestigious partners’ service,” says Stefano Lo Priore, Founder and CEO at Hyris. “Many medical institutions worldwide already adopted our technology, embracing the unprecedented simplicity, connectivity, and scalability of the Hyris SystemTM.”

    The rapid deployment of SARS-CoV-2 vaccines to a large proportion of the population now suggests new approaches to measure the duration of the immune response, and the potential need for vaccine boosters should be evaluated.

    “The assays used in our study rely on the quantification of CXCL10 mRNA after incubation of whole blood with SARS-CoV-2 specific peptides. The levels of induced CXCL10 transcripts correlate robustly with the IFN-gamma produced by activated antigen-specific T cells, serving as a proxy to detect cellular immunity in COVID-19 recovered and SARS-CoV-2 vaccinated subjects,” points out Ernesto Guccione, PhD, Professor of Oncological Sciences, and Pharmacological Sciences, at Icahn Mount Sinai.

    “This is particularly important after the emergence of SARS-CoV-2 variants like Omicron that evade most of the neutralizing ability of antibodies, but not that of T-cells,” continues Megan Schwarz, a graduate student at Icahn School Mount Sinai and first author of the manuscript. “Precise measurement of cellular responses underlying virus protection, therefore, represents a crucial parameter of immune defence.”

    “The solutions already present on the market are usually performed based on the traditional fluorescence methodologies typically used in the immunological domain,” adds Jordi Ochando, PhD, Assistant Professor of Oncological Sciences, Medicine (Nephrology), and Pathology, Molecular, and Cell-Based Medicine at Icahn Mount Sinai. “This research demonstrates that CXCL10 mRNA expression confirms data obtained with traditional methods (i.e., ELISpot) compared with naïve, COVID-19 convalescent and SARS-CoV-2 vaccinated subject,” he concludes.

    This study could prove a key solution to further support the scientific community playing a strategic role in facing this global challenge.

    Contact a Hyris expert to discover how to perform beyond your current diagnostic capability at info@hyris.net.

    Source: Hyris

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  • Genomelink and Sano Genetics Partner to Encourage More Consumers to Donate their DNA for Research and Get Rewarded

    Genomelink and Sano Genetics Partner to Encourage More Consumers to Donate their DNA for Research and Get Rewarded

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    SAN FRANCISCO, October 3, 2019 (Newswire.com)
    –
    ​The biotech startup, Genomelink, has announced it is partnering with genomic research and data-sharing startup, Sano Genetics, that will match consumers’ genetic information with new medical research.

    Under this partnership, consumers will get paid for contributing their time and genetic data to medical research, and will receive health benefits, including access to new treatments via clinical trials. In addition, participants will receive regular updates on the research they support and free personalized health and wellness reports based on their genetic profiles.

    Together, Genomelink and Sano Genetics will use the DNA data to research common disorders such as eczema, psoriasis, diabetes, and mental health conditions, as well as rare diseases like muscular dystrophy.

    The CEO and co-founder of Genomelink, Tomohiro Takano, says this new partnership will transform drug discovery and accelerate the growth of personalized medicine, enabling large-scale genetic and medical research without sacrificing data privacy.

    Genomelink is a web platform that enables consumers to upload their raw DNA report – for free – and discover more about their DNA identities and traits that go beyond ancestry. The consumer platform reveals more than 125 genetic traits in five categories – food and nutrition, personality, cognitive, fitness and physical traits. 

    Sano Genetics is a data-sharing platform where consumers submit their medical history and genetic data, which is matched with clinical studies that can benefit from their DNA. The biotech company matches participants with research projects that offer free genome sequencing and opportunities to try new treatments via clinical trials. Genome sequencing can typically cost more than $1000. 

    Takano says unlike traditional genetic data sharing partnerships, Genomelink and Sano Genetics have created a transparent, secure platform that allows individuals to explicitly opt in or out of different studies – and make money while doing so.

    “The process to submit your DNA is incredibly easy and fast,” said Takano. “Consumers can share as much – or as little information – as they wish. Once their DNA has been selected for research, consumers can then learn how to make money off their contribution.”

    How Consumers Benefit from Participating in Research

    Takano says it’s very simple to participate in the DNA research. Consumers upload their DNA report to Genomelink and give consent to sharing their genetic information with Sano. Consumers who are selected will be compensated for their contribution. 

    Several hundred Genomelink users have already contributed their DNA as part of a project to understand whether there is an interaction between genetics and common anti-inflammatories, such as Aspirin, in people with stomach ulcers. 

    Additionally, researchers conducting nonprofit studies at the University of Cambridge, the University of Liverpool, and Imperial College London are using this DNA data to research autism and autoimmune conditions.

    Genomelink users can also join studies run by for-profit companies, including clinical trials for eczema and psoriasis; research and development of new treatments for rare and chronic diseases; and several studies on how genetics influences the way people respond to medicines. The money participants will receive varies depending on the type of research – from $10 for a simple survey to hundreds of dollars for more complex studies. 

    In addition, participants who join for-profit studies are also eligible to receive free genetic testing, free upgrades to Genomelink premium or other non-monetary rewards, depending on the specifics of the study. 

    Takano says DNA data from Genomelink will not be used in research unless participants explicitly opt in. Both Genomelink and Sano Genetics have a strong commitment to transparency and data ownership for participants.

    “We believe partnerships like ours are the first step in researching rare diseases and disorders with no cures,” said Takano. “By donating your DNA to researchers studying diseases like diabetes and depression, we can learn more about how we can cure them and help thousands of patients around the world.”

    To learn more about this partnership and how consumers can get involved, visit https://sanogenetics.com/genomelink

    About Genomelink

    Genomelink is a graduate of Berkeley SkyDeck accelerator and backed by several investors, including Global Brain, Digital Garage, Sony Innovation Fund, IronFire Ventures and 500 Startups Japan. The web platform helps members learn about their DNA data, while ensuring ultimate transparency. It enables members to upload their raw DNA data file and discover more about their DNA identities and traits through intuitive visualization and scientific educational content. Genomelink’s dedicated science team updates its trait database weekly with curated research papers and academic literature that provides analysis for over 125 traits in five categories: food & nutrition, personality, cognitive, fitness, and physical traits. The research database enables users to discover new trait reports every week.

    The company was founded in 2017 by three Japanese founders – Tomohiro Takano, Yuta Matsuda and Kensuke Numakura – who have worked in genomics for years, including M3, Inc., DeNA, and P5, Inc., which was founded as a joint venture of SONY and Illumina.

    About Sano Genetics

    Sano Genetics is a UK-based platform for research in personalized medicine. Founded by three Ph.D. students from the University of Cambridge -  Patrick Short, Charlotte Guzzo and William Jones – the platform is free to use and gives users the option to upload existing genetic and medical data to match with research studies and clinical trials powering the future of personalised medicine.

    Media Contact:

    Mark Macias
    Phone: 646-770-0541
    Email: mmm@maciaspr.com

    Source: Genomelink

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  • Strand Life Sciences Announces the Release of Strand NGS v3.1 at ASHG 2017

    Strand Life Sciences Announces the Release of Strand NGS v3.1 at ASHG 2017

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    Strand NGS now supports large scale RNA- and small-RNA-Seq and Unique Molecular Identifiers (UMIs) for DNA-, RNA-, and small-RNA-Seq.

    Press Release
    –


    updated: Oct 17, 2017


    Orlando, FL, October 17, 2017 (Newswire.com)
    –
    Strand Life Sciences announced the latest version release of its bioinformatics flagship product, Strand NGS, at the Annual Meeting of the American Society of Human Genetics today. Two major themes in Strand NGS v3.1 address recent challenges in next generation sequencing (NGS).

    The first theme is large-scale RNA-Seq data analysis. Current cross-cohort RNA- and small-RNA-Seq studies span tens of replicates and batches across hundreds of samples, sometimes conducted across several different institutions. For such studies, Strand NGS v3.1 includes confounding variable analysis to eliminate technical effects, including batch effects; the t-SNE plot; profile and heat-map plots of gene-body coverage; and several other notable visual enhancements.

    The second new feature is support for Unique Molecular Identifiers, or UMIs, for DNA-, RNA- and small-RNA-Seq. UMI support in Strand NGS is end-to-end, spanning alignment to variant calling in DNA-Seq, and alignment to quantification in RNA- and small-RNA-Seq. The Bioo Scientific, Qiagen, and Rubicon UMI protocols are natively supported, and an intuitive interface allows the specification of custom UMI protocols.

    “For liquid biopsies and low-grade FFPE samples, UMI support in DNA-Seq enables the detection of somatic variants at low concentrations. In RNA-Seq, large-scale and UMI support can be used in single-cell-based studies that reveal tumor-cell heterogeneity, even at low concentrations”, says Dr. Vamsi Veeramachaneni, Chief Scientific Officer, Strand Life Sciences.  

    “At Strand, we are continuously working towards improving the accuracy and efficiency of NGS data analysis. Customers can look forward to Strand NGS becoming available on the cloud in the near future”, says Dr. Ramesh Hariharan, Chief Executive Officer, Strand Life Sciences.

    Visit Strand Life Sciences at ASHG booth #1017 to know more about Strand NGS v3.1 and other products and service offerings from Strand Life Sciences. Click here to access detailed agenda and v3.1 release notes. To know more about Strand NGS, visit www.strand-ngs.com. 

    About Strand Life Sciences
    Strand Life Sciences is a premier life science informatics innovation company. Founded in 2000, Strand is a leader in technology innovations for healthcare using genomics. By enhancing sequence-based diagnostics and clinical genomic data interpretation using a strong foundation of computational, scientific, and medical expertise, Strand is bringing individualized medicine to the world. To know more, visit www.strandls.com

    Source: Strand Life Sciences

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