McGowan Institute?
October 2008 | VOL. 7, NO. 10 | www.McGowan.pitt.edu
McGowan Institute Welcomes Distinguished Lecturer Caplan
The McGowan Institute Distinguished Lecture Series welcomed Arnold I. Caplan, PhD on October 23, 2008. Dr. Caplan is Professor of Biology and of General Medical Sciences (Oncology) at Case Western Reserve University in Cleveland. The topic of his lecture was “Adult Mesenchymal Stem Cells: New Cell-Based Therapies for Regenerative Medicine.”
Dr. Caplan is known as a pioneer in the fields of developmental biology and regenerative medicine due to his identification of mesenchymal stem cells and the establishment of certain correlating fundamentals in cell biology. He received his B.S. in chemistry from the Illinois Institute of Technology in Chicago. From there he went to The Johns Hopkins University Medical School in Baltimore, where he received his PhD in Physiological Chemistry and completed his postdoctoral fellowship. He furthered his postdoctoral training at Brandeis University in Boston. In 1969 Dr. Caplan started at Case Western Reserve University as a member of the faculty, and he became Professor of the Department of Biology in 1981. Today, Dr. Caplan is the Director of the Skeletal Research Center, and he is Professor in the Departments of General Medicine Sciences (Oncology), Orthopaedics and Physiology and Biology.
Following the session, lecturer and attendees enjoyed a reception and a Molecular Art Exhibit. The featured artist was Jason Shorr, whose paintings combine human anatomy with art. Mr. Shorr previously displayed as part of “Bodies…The Exhibition,” a high-profile show at the Carnegie Science Center, this past spring.
The next Distinguished Lecture will be held at the McGowan Institute’s Scientific Retreat on March 9, 2009. The lecturer will be Prof. Dr. Jeffery A. Hubbell, who is Professor of Biomedical Engineering and director of the Institute for Biomedical Engineering of the Swiss Federal Institute of Technology and Professor of Materials Science at the University of Zurich. The third Distinguished Lecture will be held on April 9, 2009, and the speaker will be Marie Csete, MD, PhD Chief Scientific Officer of the California Institute for Regenerative Medicine (CIRM).
McGowan Institute for Regenerative Medicine faculty member Constance Chu, MD, a leading researcher in cartilage degeneration, repair, and regeneration, was recently chosen as the recipient of the Albert B. Ferguson Jr., MD, Endowed Chair in Orthopaedic Surgery at the University of Pittsburgh School of Medicine.
As director of the Cartilage Restoration Program at the University of Pittsburgh School of Medicine, Dr. Chu specializes in joint replacement and cartilage repair. She is one of only a handful of board-certified orthopaedic surgeons conducting research funded by the National Institutes of Health. Her cartilage research program is recognized internationally for innovative studies integrating cellular and molecular biology along with advanced and novel imaging technologies.
Dr. Chu recently received the honor of being only the second American woman awarded the ABC Traveling Fellowship in Orthopaedics. This is the oldest and most prestigious traveling fellowship in orthopaedics and recognizes emerging academic leaders. In 2007, she received the Kappa Delta Young Investigator Award from the American Academy of Orthopaedic Surgeons in recognition of her research efforts, which have had a direct impact on the clinical practice of orthopaedic surgery.
Dr. Chu graduated from the United States Military Academy in 1983 to become the first Chinese-American woman to graduate from West Point. After a distinguished military career, she graduated from Harvard Medical School in 1992 and completed her orthopaedic residency at the University of California San Diego. She returned to Harvard for subspecialty training in joint replacement and cartilage repair at the Brigham and Women’s Hospital. She has presented at numerous international meetings, including the International Cartilage Repair Society, the Orthopaedic Research Society, and Regenerate.
Dr. Ferguson served as chair of the Department of Orthopaedic Surgery at the University of Pittsburgh School of Medicine from 1953 to 1986, where he pioneered the use of titanium and other durable materials for hip and knee replacements. He is credited with training dozens of the world’s top orthopaedic surgeons.
Congratulations, Dr. Chu!
McGowan Institute for Regenerative Medicine faculty member David H. Perlmutter, MD, scientific director and physician-in-chief at Children’s Hospital of Pittsburgh of UPMC, has been elected to the prestigious Institute of Medicine (IOM). Election to the IOM is considered one of the highest honors in the fields of health and medicine and recognizes individuals who have demonstrated outstanding professional achievement and commitment to service.
Dr. Perlmutter, the Vira I. Heinz Professor and Chair of the Department of Pediatrics at the University of Pittsburgh School of Medicine, is one of only 65 new members and five foreign associates who were announced at the IOM’s recent annual meeting. Current active members elect new members from among nominated candidates.
Since joining Children’s Hospital in 2001, Dr. Perlmutter has led an effort to expand the hospital’s basic and clinical research program so that it is ideally poised to investigate the molecular basis of pediatric disease and to develop innovative new therapies for childhood illnesses. Under his leadership, Children’s Hospital has become among the fastest growing pediatric research program in the country in terms of National Institutes of Health (NIH) funding from 2000–2005.
Dr. Perlmutter has carried out basic research on alpha-1-antitrypsin deficiency, the most common genetic liver disease of childhood, for more than 20 years. His work has led to many new concepts about the pathobiology of liver disease in this deficiency and has suggested several new concepts for chemoprophylaxis of chronic liver injury, hepatocellular carcinoma, and emphysema in this genetic disease. He is the principal investigator on three NIH grants in this area and also now holds four other NIH grants, including the Child Health Research Center of Excellence Award for training pediatric physician-scientists in the molecular basis of pediatric disease.
The IOM was established in 1970 by the National Academy of Sciences as a national resource for independent, scientifically informed analysis and recommendations on health issues. The institute provides unbiased, evidence-based, authoritative information and advice concerning health and science policy to policy-makers, professionals, leaders in every sector of society, and the public at large.
Congratulations, Dr. Permutter!
Dr. Paul Monga was named the Division Director of Experimental Pathology (previously known as the Division of Cellular and Molecular Pathology) at the University of Pittsburgh. His appointment began on September 25, 2008. The Division of Experimental Pathology is comprised of 13 core faculty who share a common goal towards “striving for improved human health by better understanding of cellular and molecular processes through applied research in disease etiology, pathogenesis, diagnosis and treatment.” Dr. Monga will act as a point of contact for members of other divisions within the department. This allows faculty who may not be primarily members of Experimental Pathology to share common interests and participate in joint endeavors. He will communicate with all faculty in this category and work to achieve better integration of effort and purpose.
In addition to this honor, Dr. Monga was asked by the NIH to serve as a study section member for Hepatobiliaty Pathophysiology. His term started on July 1, 2008 and continues for four years. Dr. Monga has also been named as Associate Editor for the American Journal of Pathology, which is the leading journal in the field of cellular, molecular, and experimental pathology. Also, Dr. Monga is now on the editorial board of the journals Hepatology and Organogenesis. He was elected the Program Chair for the American Society of Investigative Pathology, and he has accepted servicde on the Basic Research Committee for the American Society of Study of Liver Diseases (AASLD). Finally, Dr. Monga was selected by the Federation of American Societies for Experimental Biology (FASEB) to co-organize its 2010 summer research conference on liver, which will be held in Snowmass, CO.
Welcome to Yadong Wang, PhD, who has joined the Department of Bioengineering and the McGowan Institute as Associate Professor of Bioengineering. Dr. Wang earned his PhD at Stanford University in 1999, and served as Assistant Professor at Georgia Tech and Emory since August 2003 prior to coming to Pittsburgh in September 2008.
Dr. Wang’s interests include bio-inspired materials for cardiovascular tissue engineering, nerve regeneration, and controlled delivery of biomacromolecules. His laboratory works at the interface of chemistry, materials science, and medicine. Dr. Wang’s team applies minimalistic biomimetic strategies to biomaterials design and explores means to translate cutting-edge materials innovations into clinical benefits.
McGowan Institute for Regenerative Medicine faculty member, Robert Kormos, MD, professor of surgery, University of Pittsburgh School of Medicine, and director, UPMC Artificial Heart Program, is pleased to announce that UPMC has received The Joint Commission’s Gold Seal of Approval™ for ventricular assist device (VAD) support for destination therapy, which is heart support for patients with end-stage heart disease who are not candidates for heart transplantation. Previously, VADs were primarily used as a bridge to heart transplant, but as clinical experience has demonstrated, they have become a viable treatment option for those patients with end-stage heart disease without compromising quality of life.
Since the UPMC Artificial Heart Program was developed in 1985, more than 450 patients have been supported with some type of mechanical circulatory device, many of whom went on to receive heart transplants and are still alive today. Heart pumps are used in patients whose hearts are failing, but are not suitable candidates for heart transplantation, due to age or other serious medical conditions. They provide relief and support to the heart by reducing cardiac workload and allowing the heart to rest. In some instances, heart pumps can also be used as a “bridge to heart transplantation,” until a suitable organ can be found.
McGowan Institute for Regenerative Medicine faculty member Philip LeDuc, PhD, recently was named the Russell V. Trader Career Faculty Fellow in Mechanical Engineering, Carnegie Mellon University. The University’s Career Faculty Fellows are term professorships of 1 to 3 years that recognize outstanding young faculty in the college and give them the freedom to engage in creative ventures that are not readily supported by traditional granting agencies. Through their work, these young educators raise the level of performance of all around them and bring honor to the institution.
Dr. LeDuc received his PhD from Johns Hopkins University and was a post-doctoral fellow at Children's Hospital Boston and Harvard Medical School. He is in the Carnegie Mellon University Mechanical Engineering Department with courtesy appointments in Biomedical Engineering and Biological Sciences. Dr. LeDuc’s research interests are linking mechanics to biochemistry at the cellular and molecular levels through examining structural regulation. He pursues this goal through developing and utilizing nanotechnology, microtechnology, computational biology, and controls theory. Dr. LeDuc has received the National Science Foundation CAREER Award, and the Beckman Foundation Young Investigators Award, while also being selected as a faculty member for the Sloan Foundation Minority PhD Program.
Russell Trader attended just 1 year at the Carnegie Institute of Technology (c.1920) and studied Machine Construction in the College of Industries, the forerunner of Mechanical Engineering. Upon the death of his wife, Rachael, in 2000, Carnegie Mellon University received funds to establish the Russell V. Trader Career Faculty Fund in Mechanical Engineering as a lasting memorial to Russell Trader. The principal of this fund is used to provide faculty support through research, fellowships, and equipment funding.
Congratulations, Dr. LeDuc!
McGowan Institute for Regenerative Medicine faculty member Ora Weisz, PhD, professor of medicine, cell biology, and physiology, University of Pittsburgh, has been named the associate director of the Kidney Research Center. The University of Pittsburgh School of Medicine, Renal-Electrolyte Division recently announced its receipt of a nearly $4 million, 5-year Kidney Research Center grant from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), one of only eight centers in the United States.
The Center will support four main core facilities: cellular physiology, single nephron and whole organ physiology, imaging at a cellular and organ level, and the use of model organisms to elucidate novel aspects of kidney function. All research cores are structured to serve as nationwide resources for investigators.
The Kidney Research Center also will support 2-year pilot research projects that are currently led by Linton Traub, PhD, associate professor of cell biology and physiology; Agnes Swiatecka-Urban, MD, assistant professor of pediatrics; and Kenneth Hallows, MD, PhD, assistant professor of medicine, cell biology, and physiology.
Thomas R. Kleyman, MD, chief of the renal-electrolyte division and professor of medicine, cell biology, and physiology, and pharmacology and chemical biology at the University of Pittsburgh, will serve as director of the Center.
McGowan Institute for Regenerative Medicine faculty members Johnny Huard, PhD and Burhan Gharaibeh, PhD, along with investigators at the Stem Cell Research Center (SCRC), utilize a modified preplate technique, which separates cells based on their adhesion characteristic to collagen coated flasks, to isolate a population of muscle-derived stem cells (MDSCs). The ability of MDSCs to proliferate in vitro and in vivo for an extended period of time combined with their strong self-renewal ability and impressive multipotency suggests that MDSCs are a unique cell population that could significantly improve the efficiency of muscle cell-mediated therapies for tissue engineering applications to improve bone and cartilage healing as well as improve skeletal and cardiac muscle regeneration.
Recently, SCRC researchers used fluorescence-activated cell sorting (FACS) to isolate several populations of human muscle-derived cells from adult human skeletal muscle, which included two populations of human muscle-derived blood vessel cells. These populations included pericytes and a novel population of cells that co-express myogenic and endothelial cell markers (myoendothelial cells). These myoendothelial (myo-endo) cells and pericytes have been shown to display a regenerative capacity in skeletal and cardiac muscles greater than that shown by human myoblasts and are therefore considered to be a human equivalent population to the murine MDSCs.
SCRC researchers are also interested in comparing the two human vascular-derived muscle cell populations (pericytes and myo-endo cells) to the same cells transduced as iPS cells. These populations will be compared for their regenerative potential, tolerance to oxidative stress, and their propensity to form tumor when implanted into certain tissues. By activating specific genes, researchers have the ability to increase a cell’s pluripotency and proliferative and regenerative capacities, but also increase the potential of the cells to undergo neoplastic transformation. Using iPS technology gives scientists a powerful tool to dissect the delicate balances between stem cells and cancer stem cells. Furthermore, Drs. Huard and Gharaibeh believe that the use of the iPS technology will greatly facilitate cell and gene therapy for use in regenerative medicine, especially human disease-specific iPS cells (e.g., iPS cells from Duchenne Muscular Dystrophy patients).
Dr. Huard of the University of Pittsburgh is a professor in the Departments of Orthopaedic Surgery, Molecular Genetics, Biochemistry, Bioengineering, and Pathology, and is also the director of the Stem Cell Research Center. He has been named the Henry J. Mankin Endowed Chair in Orthopaedic Surgery Research. Dr. Huard is also deputy director for cellular therapy at the McGowan Institute for Regenerative Medicine and an associate director of the Pittsburgh Tissue Engineering Initiative (PTEI). Dr. Gharaibeh is a research assistant professor within the Stem Cell Research Center, part of the Department of Orthopedic Surgery at the University of Pittsburgh.
McGowan Institute for Regenerative Medicine faculty member J. Peter Rubin, MD, director of the Life After Weight Loss program, a clinical center at the University of Pittsburgh dedicated to the comprehensive care of patients after surgical or medical weight loss treatments, is a recognized national leader in the field of body contouring. Dr. Rubin and his program staff have pioneered surgical techniques in support of the many patients who experienced bariatric surgery and must later deal with remaining folds of skin and tissue after extreme weight loss.
Dr. Rubin is known as the father of the "bra lift," a surgical procedure that uses the patient's own tissue to create an internal brassiere that better supports the new shape of the breast. Additionally, tissue from the side of the chest is used both to increase breast size and eliminate extra skin alongside it.
Life After Weight Loss is a unique program that combines body contouring surgery with lifestyle and nutritional counseling in a supportive environment. There are many factors that contribute to both long-term weight loss success and favorable outcomes in plastic surgery. Dr. Rubin and his trained staff work with patients to help evaluate and optimize these factors. Staff members include researchers, medical weight management specialists, psychological and behavioral specialists, and a nutritionist. The program also includes visiting fellows, who stay for a year.
As an accomplished medical researcher, Dr. Rubin’s keen understanding of scientific methods helps him deliver superior care to his patients. He has published extensively in the scientific literature and has received numerous academic awards. His groundbreaking work in the field of adipose biology holds the promise of leading to new clinical treatments for fat tissue. His work is funded by the National Institutes of Health. Also, Dr. Rubin is the recipient of the Presidential Early Career Award for Scientists and Engineers, recognizing the most promising scientists in the nation.
McGowan Institute for Regenerative Medicine faculty member Stefan Schneeberger, MD, General and Transplant Surgeon and Visiting Research Assistant Professor of Surgery, University of Pittsburgh Thomas E. Starzl Transplantation Institute, has a primary clinical as well as research interest in hand transplantation. Based on a background in clinical hand transplantation, he is investigating strategies to minimize immunosuppression in composite tissue allotransplantation (CTA) in experimental settings. In this context, he specifically addresses the skin, which has been shown to be the primary target for rejection, and combines this approach with novel concepts that allow for minimization of systemic immunosuppression. It is his distinct goal to develop a clinically relevant treatment protocol for CTA in order to make it a therapeutic option for all patients that could benefit from such a procedure.
CTA is the transplantation of a composite of more than one tissue (example: nerves, skin, muscles, tendons, bones, cartilage, and fat) between individuals of the same species. Worldwide, several types of CTA are now being done or are considered good candidates to be done in the future. Successful surgeries to date include hand, double arm, double forearm, partial face, and partial abdominal wall transplants. Other CTA possibilities include the scalp, ears, genitalia, and body wounds. Most, if not all, of these would only seem appropriate when risks from taking immunosuppressive drugs have been significantly reduced.
Although CTA recipients have all been adults so far, Dr. Schneeberger believes that eventually it might be especially useful in treating birth defects.
David J. Hackam, MD, PhD, Assistant Professor in the Cell Biology and Physiology department and in the Department of Surgery at the University of Pittsburgh, School of Medicine, received a Ro1 grant of $1,704,375 from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and the National Institutes of Health (NIH) to study the modulation of TLR4 and TLR9 signaling in necrotizing enterocolitis (NEC). The long term goal of the project is to understand the pathogenesis and to design novel therapeutic approaches for NEC, which is the leading cause of death from gastrointestinal disease in preterm infants and is characterized by mucosal disruption and the translocation of lipopolysaccharide (LPS) across the inflamed intestine. Dr. Hackam’s team have recently demonstrated that the LPS receptor – Toll like receptor 4 (TLR4) – plays a critical role in the pathogenesis of NEC. Activation of TLR4 on enterocytes by LPS leads to an increase in enterocyte apoptosis and villus loss, as well as reduced intestinal repair by blocking intestinal restitution and proliferation, leading to mucosal disruption. They have also shown that mice with mutations in TLR4 are protected from the development of NEC and accordingly demonstrate reduced apoptosis and enhanced intestinal healing. These findings suggest the possibility that TLR4 may be a useful therapeutic target in NEC.
The NIH has renewed funding on the Levitronix Phase II Small Business Innovation Research (SBIR) grant in the amount of $586,841. This brings the award total for the two years to $1,068,957. The grant was originally awarded to Dr. Harvey Borovetz, who spearheaded the project in partnership with other scientists and two medical device manufacturers. Included in the project as Co-Investigators are Dr. William Wagner, Dr. Marina Kameneva, Dr. Peter Wearden, Dr. Steven Webber, and Dr. Victor Morell. The SBIR, which is entitled "Development of a Magnetically Driven Heart Pump", seeks to address an unmet need for mechanical circulatory support in children with heart failure. Pediatric heart patients possess several unique features, such as small body size, reduced blood volume, and altered hemodynamic properties, which distinguish them from adults with heart failure. The project seeks to account for these features by developing a miniature, low-cost, centrifugal ventricular assist device for use as an extracorporeal mechanical support system. The approach features a magnetically levitated, and thus friction-less, rotor/stator configuration, which efficiently generates flow with minimum hemolysis. The major advantages of the current design are its small and relatively simple extracorporeal design, its ability to efficiently regulate pump output over a large range of flow conditions, and its ease of production. Once it reaches clinical use, this pioneering effort will offer opportunities to help young children through challenging days until other therapies can correct their cardiac problems.
It is with great sadness that we report the loss of Dr. Robert M. Rogers, Professor of Pulmonary, Allergy, and Critical Care Medicine and Director of the Comprehensive Lung Center at the University of Pittsburgh Medical Center. Dr. Rogers passed away on Thursday, September 4, 2008. A native of Pennsylvania, he received his Bachelor's degree from LaSalle University in 1956 (cum laude) and his M.D. from the University of Pennsylvania in 1960. He pursued an internship at the Hospital of the University of Pennsylvania and his internal medicine training at University Hospitals of Cleveland. Dr. Rogers completed fellowships in pulmonary disease at Case Western Reserve University, Cleveland, and at the Hospital of the University of Pennsylvania. He was the recipient of many honors, including the Presidential Award of the American Thoracic Society, Special Recognition Award from the American College of Chest Physicians, and the Outstanding Service Award from the Pennsylvania Thoracic Society. His interest and expertise extended to asthma, chronic obstructive lung disease and emphysema, pulmonary alveolar proteinosis, adult respiratory distress syndrome, sleep related disorders of breathing, and sarcoidosis.
In both his clinical practice and his investigative research, Dr. Rogers brought much energy and compassion to his work. Our deepest sympathies go out to his family. Dr. Rogers will be missed.
The Regenerative Medicine Podcasts continue to gain listeners and explore pertinent topics. Remember to tune in and keep abreast of new interviews. The most recent podcasts are:
#57 – Kerem Pekkan, PhD – Dr. Pekkan, an Assistant Professor of Biomedical Engineering at Carnegie Mellon University, uses experimental and computational fluid mechanics in complex anatomical morphologies combined with image modalities and acquisition to address important clinical issues that are in the area of fluid mechanics related to congenital heart diseases. His research interests include biomedical and bio-fluid dynamics, cardiovascular flows, and circulation. His research also utilizes bioreactors and in vitro cell and tissue culture systems.
#58 – John Manzetti, MBA – Mr. Manzetti is the President and Chief Executive Officer of Pittsburgh Life Sciences Greenhouse (PLSG). He overviews the focus and achievements of the PLSG. Mr. Manzetti earned his Bachelor’s degree in Business Administration from Geneva College and his MBA from the University of Akron.
Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews.
| Authors: | Stergios Moschos, Maja Mandic, John Kirkwood, Walter Storkus, and Michael Lotze |
| Title: | Current and Future Considerations in the Use of Mechanical Circulatory Support Devices |
| Summary: | Heart failure (HF) is a major public health problem in the United States, and its prevalence is likely to increase with the aging U.S. population. Mechanical circulatory support (MCS) utilizing bladder-based blood pumps generating pulsatile flow has been reserved for patients with severe HF failing medical therapy. As MCS technology has advanced to include rotary blood pumps, so has our understanding of the biological and clinical responses to MCS, which in turn has altered the risk/benefit profile of this therapy. This may lead to paradigm shifts in device usage from support of end-stage HF to temporary support for recovery of cardiac function and earlier usage, to, ultimately, prevention of disease progression. This review serves to explore the current state and future opportunities of MCS within our larger understanding of the epidemiology, pathophysiology, and treatment options for HF. |
| Source: | Annual Review of Biomedical Engineering; Vol. 10: 59-84; August 2008 |
PI |
William Federspiel, PhD |
Co-Investigators |
Alan Russell, PhD and William Wagner, PhD |
Title |
Percutaneous Respiratory Assist Catheter |
Description |
Each year several hundred thousand Americans suffer short term lung failure requiring respiratory support within the intensive care unit. The objective of this proposal is to develop a percutaneous respiratory assist catheter (PRAC) that can be inserted into the venous system to provide supplemental breathing support, independent of the lungs, for patients requiring short-term (~ 4-7 day) respiratory assistance. The PRAC will be designed for percutaneous insertion into a peripheral vein and placement in the central venous system, where it will be exposed to all the blood returning to the heart. The PRAC will use a rotating impeller within the fiber bundle to generate active mixing of blood to enhance gas exchange. We will also develop novel hollow fiber membranes that incorporate immobilized enzymes that will further accelerate CO2 removal. The target is a percutaneous assist catheter (20-25 Fr or smaller) that can provide 90-120 ml/min of CO2 removal when used as an adjuvant or replacement to existing therapy for patients with acute lung failure (ARDS, pneumonia) or acute on chronic lung failure (COPD with exacerbation). |
Source |
NIH |
Term |
07/08/08 – 05/31/12 (this award); 04/01/02 – 05/31/12 (entire project) |
| Amount: | $1,350,174 (this award); $2,798,136 (entire project) |
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