Cellular Therapy

The dopamine D2 receptor has a previously unobserved role in modulating Wnt expression and control of cell proliferation, according to a new study from the George Washington University (GW) and the University of Pittsburgh. The research, published in Scientific Reports, could have implications for the development of new therapeutics across multiple disciplines including nephrology, endocrinology, and psychiatry.  Zachary Freyberg, MD, PhD, an assistant professor of psychiatry and cell biology at the University of Pittsburgh School of Medicine and an affiliated faculty member of the McGowan Institute for Regenerative Medicine, is a senior author on the study.

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Magee-Womens Research Institute (MWRI) has received $112,500 in funding from A Glimmer of Hope Foundation (GOH) to further research of metastatic breast cancer (MBC) and to enhance patient support services at UPMC Magee-Womens Hospital.

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To commemorate Hypophosphatasia Awareness Day (October 30), Soft Bones, Inc., an organization dedicated to providing information, education and support to those affected by hypophosphatasia (HPP), awarded its tenth annual Maher Family Grant.  In commemoration of its tenth anniversary, Soft Bones awarded two grants for the first time ever.  McGowan Institute for Regenerative Medicine affiliated faculty member Dobrawa Napierala, PhD, Associate Professor of Oral Biology at the Center for Craniofacial Regeneration, University of Pittsburgh School of Dental Medicine, is one of this year’s awardees and will study adolescents and adults with HPP.

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According to the American Cancer Society, kidney cancer is among the top ten most common cancers in men and women, and clear cell renal cell carcinoma (ccRCC) – the most common subtype of tumor associated with kidney cancer – accounts for more than 75 percent of cases.

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The University of Pittsburgh’s Center for Medical Innovation (CMI) awarded grants totaling $70,000 to three research groups through its 2019 Round-1 Pilot Funding Program for Early Stage Medical Technology Research and Development. McGowan Institute for Regenerative Medicine affiliated faculty member Carl Snyderman, MD, MBA, is a co-investigator on one of the selected projects, along with Garrett Coyan, MD, a surgery resident in the lab of William Wagner, PhD:

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Researchers of Sechenov University and University of Pittsburgh—including McGowan Institute for Regenerative Medicine affiliated faculty members

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A new report highlights the latest advances in cell-based therapies for the treatment of disorders of the musculoskeletal system, such as arthritis and osteoporosis, and it identifies key unanswered questions that should be addressed through ongoing research. The report is published in the Journal of Bone and Mineral Research and concurrently in the Journal of Orthopaedic Research, and was issued by a joint Task Force of the American Society for Bone and Mineral Research and the Orthopaedic Research Society.  McGowan Institute for Regenerative Medicine affiliated faculty member Rocky Tuan, PhD, Vice-Chancellor and President of The Chinese University of Hong Kong and the former Associate Director of the McGowan Institute, is the co-chair of the Task Force.

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Researchers from Carnegie Mellon University (CMU) and Nanyang Technological University, Singapore (NTU Singapore) have developed an organ-on-an-electronic-chip platform, which uses bioelectrical sensors to measure the electrophysiology of the heart cells in three dimensions. These 3D, self-rolling biosensor arrays coil up over heart cell spheroid tissues to form an “organ-on-e-chip,” thus enabling the researchers to study how cells communicate with each other in multicellular systems such as the heart.

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As reported by Forbes contributor Robin Seaton Jefferson, LyGenesis, Inc., hopes to enter human trials in 2020 on a therapy that could potentially give patients with end stage liver disease hope for new livers without having to wait on donated organs. The technology, developed through research from McGowan Institute for Regenerative Medicine faculty member Eric Lagasse, PharmD, PhD, associate professor in the Department of Pathology at the University of Pittsburgh and LyGenesis’ Chief Scientific Officer, uses lymph nodes as bioreactors to regrow functioning organs within a patient’s own body. The research found that a variety of different cells types and tissues, including the liver, could engraft and actually grow within lymph nodes. The company is working on injecting cadaver cells into lymph nodes to grow secondary livers.

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Study: In the time it takes you to read this sentence, every cell in your body suffers some form of DNA damage. Without vigilant repair, cancer would run rampant, and now scientists at the University of Pittsburgh have gotten a glimpse of how one protein in particular keeps DNA damage in check.

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The McGowan Institute has formed an alliance with the International Space Station (ISS) U.S. National Laboratory to develop and demonstrate how microgravity can improve regenerative medicine-based therapies. The ISS provides a unique platform to conduct studies in a microgravity environment.

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Researchers at the University of Pittsburgh School of Medicine—including McGowan Institute for Regenerative Medicine affiliated faculty members Alejandro Soto-Gutierrez, MD, PhD, associate professor of pathology at Pitt’s School of Medicine and faculty member of the Pittsburgh Liver Research Center, and Ira Fox, MD, professor of surgery and pediatric transplantation at UPMC Children’s Hospital of Pittsburgh—are the first to grow genetically modified miniature human livers in the laboratory, to emulate human liver disease progression and test therapeutics.

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Two Carnegie Mellon University (CMU) faculty members are changing the way that proteins are made for industry through their startup BioHybrid Solutions. McGowan Institute for Regenerative Medicine affiliated faculty member Krzysztof Matyjaszewski, PhD, is the J.C. Warner University Professor of Natural Sciences in the Department of Chemistry, and Alan Russell, PhD, is the Highmark Distinguished Career Professor of Chemical Engineering and former Director of the McGowan Institute.

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Patients at UPMC Salvator Mundi International Hospital in Italy will soon have increased access to innovative methods of tissue regeneration that could improve healing and outcomes with reconstructive or aesthetic plastic surgery.

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An international group of scientists in the joint study of the laboratory of the Wistar Institute, University of Pittsburgh, and I.M. Sechenov First Moscow State Medical University discovered the change in activity of one of the immune cells types called neutrophils during cancer development: They begin to prevent other immune cells from fighting tumors, and thus decelerate treatment. The scientists found protein causing such changes and demonstrated that suppressing its activity in the cells delays cancer development. The research details are published in Nature.  McGowan Institute for Regenerative Medicine affiliated faculty member Valerian Kagan, PhD, Professor and Vice-Chairman in the Department of Environmental and Occupational Health as well as a Professor in the Department of Pharmacology and Chemical Biology, the Department of Radiation Oncology, and the Department of Chemistry at the University of Pittsburgh, and also the Director of the Center for Free Radical and Antioxidant Health, is a co-author of the study.

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The same sources thought to inflict oxidative stress on cells—pollution, diesel exhaust, smoking and obesity—also are associated with shorter telomeres, the protective tips on the ends of the chromosomal shoelace.

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Starfish can repair injured arms and reptiles can regrow severed tails; from bacteria to humans, every species is capable of regeneration, albeit to variable extents. These functions help make species more resilient, but how can we apply the knowledge of these regenerative mechanisms to improve human health? The University of Pittsburgh Department of Bioengineering has been collaboratively working to address this question through research efforts in tissue engineering and regenerative medicine.

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In a follow-up to the recent McGowan Institute for Regenerative Medicine Scientific Retreat Panel Discussion, “Hope vs. Hype of Stem Cell Therapy,” J. Peter Rubin, MD, Chair of the Department of Plastic Surgery, the UPMC Endowed Professor of Plastic Surgery, Director of UPMC Wound Healing Services, and Professor of Bioengineering at the University of Pittsburgh, was a guest on Pittsburgh’s NPR News Station WESA program, The Confluence.

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McGowan Institute for Regenerative Medicine affiliated faculty member Joseph Glorioso III, PhD, Co-founder, CODA Biotherapeutics, and Professor and Emeritus Chair, Department of Microbiology and Molecular Genetics, University of Pittsburgh School of Medicine, is working on a gene therapy approach for treating chronic pain.  CODA is developing engineered neurotransmitter receptors that are activated exclusively by orally bioavailable drugs to control the activity of hyperexcitable neurons responsible for chronic neuropathic pain. The gene encoding the receptor is delivered to dysfunctional neurons by proprietary viral vectors that are optimized for robust and targeted gene transfer. Standard neurosurgical procedures are used to administer these viral vectors directly to the neurons to be controlled. Once expressed, the engineered receptor can be activated by the drug to modulate neuronal activity. This enables the selective, tunable and reversible regulation of the receptor – and hence cellular activity – based on the dosing regimen of the drug. CODA is engineering receptors to have exquisite sensitivity for the pharmacological activator, which should dramatically limit off-target side effects that plague many pharmaceutical treatments.

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Do lymph nodes hold the key to regenerating failed organs?

Our body’s lymph nodes generally go unnoticed, unless they become swollen and painful in the fight against infection. They’re part of a body-wide system that quietly grows immune cells, circulates them to infection sites, and carries away waste.

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Our cells sometimes have to squeeze through pretty tight spaces. And when they do, the nuclei inside must go along for the ride. Using super-sensitive microscopic imaging, a team of scientists from the University of Pittsburgh and Carnegie Mellon University have made a fundamental biological discovery that explains the structure of the nuclear envelope and gives tantalizing clues as to how cells squish through narrow openings without springing a leak.

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In animal models and patient tissues, researchers from the University of Pittsburgh School of Medicine—including McGowan Institute for Regenerative Medicine affiliated faculty members Satdarshan “Paul” Monga, MD, professor of pathology and the founding director of the Pittsburgh Liver Research Center at Pitt’s School of Medicine, and Michael Oertel, PhD, assistant professor of pathology and a member of the Pittsburgh Liver Research Center —have identified a new molecular pathway in the liver that suggests a commonly used anti-rejection medication could be repurposed to treat certain liver cancers.

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Voyager Therapeutics, Inc., a clinical-stage gene therapy company focused on developing life-changing treatments for severe neurological diseases, announced dosing of the first patient in RESTORE-1, a Phase 2, randomized, double-blind, placebo-controlled trial evaluating the safety and efficacy of VY-AADC for the treatment of Parkinson’s disease in patients with motor fluctuations that are refractory to medical management.

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During a coronary bypass procedure, surgeons redirect blood flow using an autologous bypass graft, most often derived from the patient’s own veins. However, in certain situations where the patient does not have a suitable vein, surgeons must rely on synthetic vascular grafts which, while life-saving, are more prone to clot formation that eventually obstructs the graft.

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Researchers in Pittsburgh—led by McGowan Institute for Regenerative Medicine affiliated faculty member Bernhard Kühn, MD—are regenerating pediatric heart tissue, potentially leading to novel approaches for the treatment of heart failure. But heart tissue doesn’t normally regenerate — so how are they doing it?

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Julie Grant, reporting for Pittsburgh’s local CBS affiliate, KDKA, recently visited with McGowan Institute for Regenerative Medicine affiliated faculty member George Gittes, MD, Director of the Richard King Mellon Foundation Institute for Pediatric Research and Co-Scientific Director at UPMC Children’s Hospital of Pittsburgh of UPMC.  She learned that reversing autoimmune type 1 diabetes without immunosuppression has proven to be extremely difficult, but Dr. Gittes and researchers at Children’s Hospital and the University of Pittsburgh School of Medicine have achieved that outcome in pre-clinical trials with an engineered, safe virus that does gene therapy.

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McGowan Institute for Regenerative Medicine affiliated faculty member Steffi Oesterreich, PhD, professor of pharmacology and chemical biology and co-director of the Women’s Cancer Research Center at UPMC Hillman Cancer Center and Magee-Womens Research Institute, is one of four leading UPMC Hillman Cancer Center breast cancer researchers that are among the world’s top scientists to share in a record-breaking $63 million investment in cancer research by the Breast Cancer Research Foundation (BCRF).

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Peptilogics’ is part of the LifeX™ Ventures company foundry, which builds life science companies from its Pittsburgh headquarters. McGowan Institute for Regenerative Medicine affiliated faculty member Dietrich Stephan, PhD, is Professor and Chairman of the Department of Human Genetics at the University of Pittsburgh and CEO of LifeX^TM Ventures.

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McGowan Institute for Regenerative Medicine affiliated faculty member Kathryn Whitehead, PhD, assistant professor of chemical engineering at Carnegie Mellon University (CMU), has been awarded a 2018 National Institutes of Health (NIH) Director’s New Innovator Award for her project titled “Fate, Function, and Genetic Engineering of Breast Milk Cells for Infant Therapy.” NIH Director’s Awards are prestigious awards given to exceptionally creative scientists proposing high-risk, high-impact research.

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In 2017, the University of Pittsburgh School of Dental Medicine received an $11.7 million grant from the National Institute of Dental and Craniofacial Research (NIDCR) to establish a resource center dedicated to advancing therapies for regenerating damaged dental, oral, and craniofacial tissues.  Officially named the Michigan-Pittsburgh-Wyss Regenerative Medicine (MPWRM) Resource Center: Supporting Regenerative Medicine in Dental, Oral, and Craniofacial Technologies, Pitt established the center in partnership with the University of Michigan and Harvard University as part of the NIDCR’s Dental, Oral, and Craniofacial Tissue Regeneration Consortium (DOCTRC). The goal of the consortium is to guide new therapies from the research stages through preclinical studies and into human clinical trials.

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The need for liver transplantation is expected to rise by 23 percent over the next two decades, but the supply of transplantable livers is inadequate today, leaving patients in need of liver transplantation with increasingly longer waiting periods and worse prospects for survival. To save the lives of more patients suffering from liver diseases, patients, their families, doctors, and researchers are all looking toward improving liver cell transplantation using autologous (patient-donated) liver cells.

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Before the United Network for Organ Sharing, or UNOS, made the heart and lung transplantation organ allocation change in November 2017, the United States was divided into 58 local donor service areas. People on the heart and lung transplant list were first matched with donors within their service areas, even if another potential match was closer geographically.

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In her report, Elaine Vitone, PittMed, writes of the numerous research efforts of Pitt investigators that are illuminating a kind of cell death called ferroptosis, which likely plays a role in many acute and chronic diseases.  Ferroptosis is a type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides and is genetically and biochemically distinct from other forms of regulated cell death such as apoptosis.

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Medtronic, a global leader in heart valve therapies, recently announced new data presented at the 30th Transcatheter Cardiovascular Therapeutics (TCT) conference, the annual scientific symposium of the Cardiovascular Research Foundation. During the meeting, investigators—including McGowan Institute for Regenerative Medicine affiliated faculty member Thomas Gleason, MD, the Ronald V. Pellegrini Endowed Professor of Cardiothoracic Surgery and Chief, Division of Cardiac Surgery of the University of Pittsburgh School of Medicine, Co-Director of the Heart and Vascular Institute at UPMC, Director of the Center for Thoracic Aortic Disease, Co-Director of the Center for Heart Valve Disease, and member of the Center for Vascular Remodeling and Regeneration at Pitt—presented the longest-term data to-date from the CoreValve U.S. Pivotal Trial

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Cut off a salamander’s tail and, in a few weeks, a near-perfect replacement grows. Do the same to a lizard and a new tail will regrow, but it won’t be the same as the original. By comparing tail regeneration between the two animals, researchers at the University of Pittsburgh School of Medicine found that stem cells in the spinal cord are the ultimate limiting factor.  McGowan Institute for Regenerative Medicine affiliated faculty members Thomas Lozito, PhD, Assistant Professor in Pitt’s Department of Orthopaedic Surgery and the Center for Cellular and Molecular Engineering, and Rocky Tuan, PhD, Vice-Chancellor and President of The Chinese University of Hong Kong, are co-authors on the study.

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Alliance for Cancer Gene Therapy (ACGT), the nation’s only charitable organization dedicated exclusively to funding cancer cell and gene therapy research, announced the recipients of its 2018 research grants using innovative clinical approaches to find gene therapy treatments for solid cancers.  One of the projects funded is a collaborative effort by McGowan Institute for Regenerative Medicine affiliated faculty member Joseph Glorioso, MD, PhD, Professor in the Department of Microbiology and Molecular Genetics in the School of Medicine with a secondary appointment in the Department of Human Genetics, of the University of Pittsburgh, and Gary Cohen, PhD, of the University of Pennsylvania, who are working together on a vaccine for melanoma.

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The lab of McGowan Institute for Regenerative Medicine affiliated faculty member Michel Modo, PhD, Professor in the Department of Radiology at the University of Pittsburgh with secondary appointments in the Department of Bioengineering and the Center for Neural Basis of Cognition, recently published a paper in Scientific Reports that characterizes the biomechanics aspects of cell injections into the brain. Dr. Modo shares the paper with the regenerative medicine community as it conceptualizes the delivery of therapeutic products through a small-bore needle, an issue commonly neglected for these types of therapies.  The abstract of the paper reads:

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Mario Cattabiani III, The Pitt News, recently reported on University of Pittsburgh’s first-ever Seed Grants.  Pitt received 171 applications and from that group selected 23 projects for awards, granting a total of approximately $1 million.  One project selected was submitted by McGowan Institute for Regenerative Medicine affiliated faculty member, Kurt Weiss, MD, Associate Professor of Orthopaedic Surgery in the University of Pittsburgh School of Medicine, Department of Orthopaedic Surgery, Division of Musculoskeletal Oncology, who received a $50,000 grant to fund the Pittsburgh Sarcoma Research Collaborative, or PSaRC — a project that will aim to develop new therapeutic strategies and eventually improve sarcoma patient care and outcomes.

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The microJoint, a three-dimensional model that replicates a human joint on a small scale, is under development in Pittsburgh. Once completed, it could have the potential to revolutionize the treatment of conditions related to joint complications, such as osteoarthritis. A radically new way of thinking — and a culture that encourages risk-taking — were key to its development.

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With cardiovascular disease on the rise and costs heading to $1 trillion in the U.S., groundbreaking developments in diagnostics, treatments and care are urgently needed. To assure that effective innovations are rapidly introduced into the health care system to benefit patients, and with evidence to demonstrate their impact, the American Heart Association, together with Philips and UPMC, announced recently the launch of Cardeation Capital, a $30 million collaborative venture capital fund designed to spur health care innovation in heart disease and stroke care. Managed by Aphelion Capital, each of the three organizations has committed $10 million to the fund to bring products and solutions to market that address critical areas of health care delivery and health management.

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