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.
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.
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.
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.
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.
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.
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.
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.
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?
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.
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).
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 LifeXTM Ventures.
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.
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.
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.
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.
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.
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
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.
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.
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:
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.
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.
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.
Life-threatening cardiac arrhythmias often occur after a heart attack, as the scar tissue can interfere with the spread of electrical impulses that activate the heart. An international research team under the leadership of the University Hospital Bonn in collaboration with colleagues from the Cornell University and the University of Pittsburgh has now developed a method to improve electrical transmission in the heart by transferring a single gene, connexin43, to cells that form the infarct scar. The results are now published in Scientific Reports. McGowan Institute for Regenerative Medicine affiliated faculty member Guy Salama, PhD, Professor within the Department of Medicine, Division of Cardiology at the University of Pittsburgh School of Medicine, is a co-author on the study.
Organogenesis is the process by which internal organs are formed. This complex biological process takes place during the embryonic phase but, in some cases, is reactivated during regenerative processes like after an hepatectomy when the liver regenerates. In the lab of McGowan Institute for Regenerative Medicine faculty member Eric Lagasse, PharmD, PhD, Associate Professor in the Department of Pathology, University of Pittsburgh, with a secondary appointment in Pitt’s Clinical and Translational Institute, and Director of the Cancer Stem Cell Center at the McGowan Institute, researchers are working on a new paradigm for tissue remodeling and eventually organogenesis, by using lymph nodes as in vivo bioreactors to grow tissue or organ substitutes. Currently, the laboratory is involved in several tissue-remodeling experiments and more specifically in developing an ectopic liver in the lymph node.
Carnegie Mellon University researchers—including McGowan Institute for Regenerative Medicine affiliated faculty member Krzysztof Matyjaszewski, PhD—have developed methods that speed up the process of developing chemically linked synthetic and biological molecules by more than 10 times in natural conditions. The findings, which marry biology and chemistry, could make the production of bioconjugates for use in biomedicine, materials science, and other fields more efficient and cost effective.
If you’re an immune cell gearing up to fight cancer, you’d better eat your breakfast. The tumor microenvironment is a harsh place, and tumor cells are ready to wear you out.
The Chuck Noll Foundation for Brain Injury Research awarded more than $600,000 in grants to five research teams at the University of Pittsburgh, Carnegie Mellon University, and UPMC in its first-year distribution.
As reported by Casey Tingle, staff writer for Orthopedics Today, ankle cartilage surgeons from around the world collaborated in Pittsburgh at the International Consensus Meeting on Cartilage Repair of the Ankle, where they discussed and debated the best ways to treat ankle cartilage injuries and ultimately established a consensus to which all orthopedic surgeons can refer.
Every day, roughly 100 billion new cells are created inside the human body. These cells join trillions of older cells to form the tissues and organs we rely on to stay alive. Sometimes when a cell is created, a mutation occurs within its DNA, transforming the cell into something defective and potentially dangerous to the body’s internal environment. Usually, a cell will recognize its own defects and quickly terminate itself.
As we age, the risk of developing cardiovascular disease such as heart failure and atrial fibrillation increases dramatically, and the rates of these age-associated diseases are expected to rise with a rapidly aging population. A team of researchers at the University of Pittsburgh believes that a naturally occurring hormone, relaxin, can reverse some of the effects of aging on the heart to reduce these risks through inhibiting a chronic, age-associated inflammatory response termed “inflammaging”.
The University of Pittsburgh recently announced the launch of LifeXTM, an initiative that will provide expertise, capital and working space to new companies addressing the most complex challenges facing modern medicine. The 10-year goal of the project is to deliver new solutions to tackle prevalent and intractable global diseases. Led by McGowan Institute for Regenerative Medicine affiliated faculty member Dietrich Stephan, PhD, the renowned human geneticist and entrepreneur and professor and chairman of the Department of Human Genetics at the University of Pittsburgh, the initiative’s initial focus will be on cancer, Alzheimer’s, multidrug-resistant bacterial infections, obesity and diabetes, and rare genetic diseases.
Reversing autoimmune type 1 diabetes without immunosuppression has proven to be extremely difficult, but in a study published in Cell Stem Cell, researchers at Children’s Hospital of Pittsburgh of UPMC and the University of Pittsburgh School of Medicine report achieving that outcome in mice using gene therapy.
A new study from The Wistar Institute, in collaboration with the University of Pittsburgh and others, revealed the mechanism implicated in the defective function of tumor-associated dendritic cells (DCs), a specialized type of immune cells that expose the antigens on their surface to activate the T cells. The new findings explain why DCs are not effective in executing a specialized process that is required for inducing antitumor immune responses and effective cancer immunotherapy. The work was published online in Nature Communications. McGowan Institute for Regenerative Medicine affiliated faculty member Valerian Kagan, PhD, Professor and Vice-Chairman in the Department of Environmental and Occupational Health at Pitt, is a co-author on the paper.
Philanthropists Cindy and Rob Citrone, dedicated to improving outcomes for pediatric transplantation across the United States and increasing the number of organ donors, have donated $2 million to Children’s Hospital of Pittsburgh of UPMC. The Citrones will also match up to $1 million in additional donations raised for Children’s transplant program.
Our tactile senses keep us aware of our environment and are essential for the execution of natural movement. Though there have been many advances in modern prosthetic devices, the loss of sensory feedback remains an issue, and many amputees struggle with everyday movement. Lack of sensory feedback in transtibial (below-knee) amputation means that the prosthesis user must rely on their residual limb for all motor skills. Patients suffer with problems in balance control, risk of falling, and severe phantom limb pain. A University of Pittsburgh group seeks to address this need for sensory feedback in prosthetic devices.
High-intensity exercise three times a week is safe for individuals with early-stage Parkinson’s disease and decreases worsening of motor symptoms. These results are according to a new phase 2, multi-site trial led by Northwestern Medicine and University of Colorado School of Medicine scientists. The randomized clinical trial included 128 participants ages 40 to 80 years old from Northwestern University, Rush University Medical Center, the University of Colorado, and the University of Pittsburgh. McGowan Institute for Regenerative Medicine affiliated faculty member Anthony Delitto, PhD, Professor and Dean of the School of Health and Rehabilitation Sciences at the University of Pittsburgh, was a member of the Pitt team in this study. The paper was published in JAMA Neurology December 11, 2017.
Highlighted in the University of Pittsburgh School of Medicine 2017 Annual Report, six men with severe second-degree burns caused by scalding water, hot tar, gasoline, a chemical explosion, contact with a live electrical wire, and ignition of paint-can fumes have become the latest patients treated at UPMC Mercy Hospital with an innovative skin regeneration technology.
McGowan Institute for Regenerative Medicine faculty member Andrew Schwartz, PhD—Distinguished Professor of Neurobiology at the University of Pittsburgh with adjunct appointments at the Center for Neural Basis Cognition (a joint venture of the University of Pittsburgh and Carnegie Mellon University), at the Robotics Institute at Carnegie Mellon University, and at Pitt’s Department of Bioengineering and its Department of Physical Medicine and Rehabilitation—recently participated in MIT (Massachusetts Institute of Technology) Technology Review’s 17th Annual EmTech where this year’s most significant news on emerging technologies was examined. Dr. Schwartz’s session featured “For Brain-Computer Interfaces to Be Useful, They’ll Need to Be Wireless.”
