McGowan Institute?
May | VOL. 5 | www.McGowan.pitt.edu
The McGowan Institute is collaborating with the National Tissue Engineering Center (NTEC) in the development of a National Strategy on Tissue Engineering. The other partners are Carnegie Mellon University, U.S. Army Combat Casualty Care Program, University of Liverpool, Duquesne University, Georgia Institute of Technology, UK Department of Trade and Industry, University of Pittsburgh, Wake Forest University Institute for Regenerative Medicine, National Institute of Advanced Science and Technology, University of Pittsburgh Medical Center, Walter Reed Medical Center, Rieken Center for Developmental Biology, Windber Research Institute, U.S. Army Institute for Surgical Research, University of Washington, and Partners in Health Care.
As part of this collaborative effort, Dr. Anthony Atala, has formally associated with the McGowan Institute of Regenerative Medicine as an Adjunct Professor of Surgery at the University of Pittsburgh. Dr. Atala’s primary appointment is at Wake Forest University where he is the Director of the Wake Forest Institute for Regenerative Medicine.
Dr. Atala is an internationally recognized expert in tissue engineering. Dr. Atala, a pediatric urological surgeon, serves as Chairman of the Department of Urology at the Wake Forest University School of Medicine. Dr. Atala’s work focuses on growing new human tissues and organs to repair those that are diseased. His ground-breaking research has made great strides in the effort to treat, and ultimately cure, damaged or diseased organs. Using cells from the patient’s own bodies he has created urethra - tubes through which urine is excreted from the body - and implanted them into people whose own urethras were diseased or defective. Also using cells from the patient’s own bodies he has also created prototype blood vessels, bladders, wombs, muscle, and cartilage.
Dr. Atala’s research has produced five spin-off companies and more than 170 patents. He also has co-authored four textbooks, and he has spoken to groups all over the world about his work. In 2000, he received the Christopher Columbus Foundation Award for his research in creating new organs.
The University of Pittsburgh Medical Center (UPMC) is beginning a clinical trial to evaluate the safety and feasibility of a potential treatment for congestive heart failure that involves injecting a patient’s own bone marrow-derived stem cells directly into the heart muscle. The procedure is expected to be performed in five to 10 patients who are scheduled to receive a heart assist device as a bridge to organ transplantation.
The stem cell trial is one of only a handful that has been cleared by the U.S. Food and Drug Administration (FDA) for heart disease. And because most patients in the UPMC study will eventually receive transplants, the trial represents the first time researchers will be able to examine a human heart treated with stem cells, an opportunity that should help solve some of the mystery as well as resolve scientific debate about just how it is that stem cells work to improve heart function.
Despite advances that have given rise to more effective medical and surgical therapies, including the use of heart assist devices, heart disease continues to exact an economic burden and be a major cause of death in the United States. As such, researchers have looked to the potential of stem cells as a treatment for congestive heart failure and other heart disease. Laboratory studies indicating that a subset of stem cells from bone marrow can generate new heart cells and blood vessels have spawned interest in performing clinical studies. While relatively few such studies have been conducted, and most have been done abroad, preliminary results have shown that blood flow and heart function improve in patients receiving the stem cell therapy.
However, to date, there has been no research in humans that helps explain why such improvements are seen, raising questions that have become the crux of scientific debate about the mechanism and action of these cells once introduced into the heart.
“People have questioned whether stem cells take on the functional characteristics of heart cells or blood vessels, or whether they help recruit other cells and growth factors that have the ability to help regenerate heart tissue. Our study presents the unique opportunity to examine the heart several months after stem cell injections, when the patient’s native heart is removed for organ transplantation, and we’re hopeful we’ll find the answers to everyone’s questions,” noted Amit N. Patel, M.D., M.S., principal investigator of the clinical trial and director of UPMC’s Center for Cardiac Cell Therapy. Dr. Patel also is director of the Center for Cardiovascular Cellular Therapy at the McGowan Institute. This study is a follow-on to Dr. Patel’s prior studies that showed substantial promise for cardiac stem cell therapy.
UPMC plans to enroll five to 10 patients. To qualify, patients must have congestive heart failure and require implantation of a ventricular assist device (VAD) as a bridge to transplantation.
Co-principal investigator of the trial is Robert Kormos, M.D., professor of surgery at the School of Medicine, director of UPMC’s Artificial Heart Program and medical director of the McGowan Institute.
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The NIH has elected to fund a new T-32 Training Program addressing Biomechanics in Regenerative Medicine that was developed under the leadership of Michael Sacks, PhD. The goal of this training program is to provide a solid foundation upon which to build a productive and independent career in Biomechanics in Regenerative Medicine (BiRM).
This goal will be accomplished via a highly coordinated and mentored interdisciplinary training program with a combination of required and elective courses, research activities, and specialized training opportunities. The BiRM Training Program incorporates faculty from the Departments of Bioengineering, Mechanical Engineering, Orthopedic Surgery, Vascular Surgery, Urology, and the McGowan Institute for Regenerative Medicine, as well as faculty from the Mechanical and Biomedical Engineering Departments from Carnegie Mellon University. This combination of training faculty research interests and coursework will provide a rich educational experience and more numerous training opportunities for the students than could be obtained within the individual university departments.
Moreover, the breadth of research areas that span various physiological systems (cardiovascular, musculo-skeletal, and urological) allows for a unique opportunity to train students to become highly skilled problem solvers while avoiding over specialization.
Since the BiRM training program is not central to any one department, its structure permits the student a much wider choice of options with which to pursue a PhD in tissue bioengineering and regeneration. In the current departmental focus of graduate education, a PhD student in one department that wishes to perform thesis research in a laboratory in another department finds many departmental based administrative roadblocks in his/her path. The BiRM program eliminates these roadblocks and permits ever increasing educational options for the students and research collaborations. Coursework includes intensive life science and biomechanics which is utilized to provide the students with a thorough grounding in both areas. Skills acquired in these courses are combined in later courses and the trainees’ research.
Phil LeDuc, PhD has won the prestigious Beckman Foundation Young Investigator’s Award for his research proposal, "Dissecting Cell Behavior through Spatiotemporal Cellular and Subcellular Control".
The Arnold and Mabel Beckman Foundation makes grants to non-profit research institutions to promote research in chemistry and the life sciences, broadly interpreted, and particularly to foster the invention of methods, instruments and materials that will open up new avenues of research in science. The Beckman Young Investigators (BYI) Program is intended to provide research support to the most promising young faculty members in the early stages of academic careers in the chemical and life sciences.
Dr. Phil LeDuc, is a McGowan faculty member and an assistant professor in Mechanical Engineering at Carnegie Mellon University. He joins an elite class of 24 Beckman awardees selected in 2005 for opening up new avenues of research in the chemical and life sciences.
LeDuc is building new tools that merge engineering technology with both scientific and commercial applications, which include developing bionanotechnology to investigate cell responses, diagnostic tools to detect cancer and computational methods to understand molecular behavior. LeDuc, who sees the human cell as a bustling metropolis with all the parts necessary to the survival of life in an ever-changing world, is using his $264,000 Beckman award to study the astonishing diversity in mechanics, structure and function of the cell.
These technologies are useful to help physicians and scientists understand and develop more accurate targets in drug development for medical treatment.
LeDuc earned his B.S. and M.S. in Mechanical Engineering at North Carolina State University in 1990 and 1995, respectively. He obtained his Ph.D at John Hopkins University in 1995.
Prior to coming to Pittsburgh, LeDuc was a fellow at Harvard Medical School and Children’s Hospital and worked as a research associate at the Singapore-based Center for Information Enhanced Medicine. He is a member of the American Association for the Advancement of Science, the American Society of Mechanical Engineers and the American Society of Cell Biology.
His other honors include winning a National Science Foundation Career Award and being named co-founder and head of missionary work in Ghana, Africa.
Dr. Michael Chancellor has reported that a pure culture of muscle-derived stem cells (MDC) may not be needed to cure incontinence; his findings were presented at the annual meeting of the American Urological Association, and will be published in abstract 929 in the AUA proceedings.
“When isolating a specific type of cell for transplantation into the body, the common thought is that the cells must be a pure culture. Getting a pure culture of muscle-derived cells, free of contaminating fibroblasts is difficult,” said Dr, Chancellor, professor, department of urology. “But, if the fibroblasts don’t interfere with the muscle-derived cells, using these cells to regenerate muscle just got a great deal easier.”
In animal models of stress urinary incontinence, researchers injected muscle-derived cells, fibroblasts and a mixture of MDC and fibroblasts into the tissue surrounding the urethra. Prior to injection, the models showed a significant decrease in leak point pressure, the point where the bladder leaks passively. Post-injection, all three groups showed an improved leak point pressure of the surrounding urethral tissue. Four weeks post-injection, MDC, fibroblasts and the combination MDC/fibroblast mixture were still present at their respective injection sites. There were no complications.
Fibroblasts did not interfere with the MDC ability to improve leak point pressure. However, the mechanism by which leak point pressure was improved, whether it be muscle regeneration from the MDC or a bulking effect from the fibroblasts is still being investigated. Prior animal model studies by the University of Pittsburgh group have found that MDC were able to regenerate deficient urethral muscle.
In addition to Dr. Chancellor, Irmute Usiene, Ron Jankowski, Ryan Pruchnic, Dongdeuk Kwon, Johnny Huard and Fernando de Miguel, all from the University of Pittsburgh, contributed to this study.
The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases and Cook MyoSite. MORE
Also at the annual meeting of the American Urological Association (AUA) in San Antonio, Dr, Chancellor reported that he and his colleagues have isolated two biomarkers for interstitial cystitis (IC), a chronic and painful pelvic disease for which there currently is no test. The discovery of these biomarkers could lead to a definitive test for IC and have the potential to lead to new therapies.
IC is a frustrating disease for patients because, to this point, there is no accurate way of diagnosing the condition. Patients undergo a variety of tests to rule out other diseases, all while experiencing significant pain and discomfort. Only after these tests come back negative, can a doctor make the diagnosis of IC.
According to the National Institute of Diabetes and Digestive and Kidney Diseases, 700,000 Americans have IC; 90 percent are women. IC is one of the chronic pelvic pain disorders, defined by recurring discomfort or pain in the bladder and surrounding pelvic region. Symptoms vary and can include any combination of mild to severe pain, pressure and tenderness in the bladder and pelvic area; and an urgent and/or frequent need to urinate. In IC, the bladder wall may become scarred or irritated, and pinpoint bleeding may appear on the bladder wall. MORE
Researchers must be more rigorous in how they design and conduct clinical studies as well as be more mindful of the language they use to describe their findings in the scientific literature or in writing reviews of other research, asserted Dr. Kupfer in a session devoted to discussion about risk factors in medicine and psychiatry at the American Psychiatric Association Annual Meeting.
The general public may not be reading the Archives of General Psychiatry or the New England Journal of Medicine, but they are basing important health care decisions and lifestyle changes on the research findings that these and other journals publish, particularly when such findings concern risk factors. Moreover, these scientific reports frequently are interpreted by clinicians, policy makers and the news media as calls to action, only later to be refuted or questioned by conflicting studies that may even claim serious and harmful consequences from those actions.
Dr. Kupfer asks “What is a risk? What is a risk factor? Are all risk factors equal? What is the threshold for true clinical significance? The general public can’t be expected to understand these questions, let alone know the answers. Yet, ultimately, they are the ones who are most affected by journal articles that include words like ‘risk’ that even some of us working in research are not accurately defining.”
“If we are rigorous in organizing, conducting, presenting and evaluating scientific research – specifically psychiatric research – then we are taking important steps in fitting this research into the larger framework of discovering the causes and ways to prevent diseases and disorders. Researchers are on the front line of accomplishing these changes. We are responsible for the quality of the studies that we conduct and for the interpretation of our studies to the media, the general public and our colleagues. These new standards are aimed at raising the bar and will ultimately encourage well-designed and correctly interpreted research that will help in our shared goal of advancing science,” said Dr. Kupfer. MORE
Freddie H. Fu, M.D has been elected second vice president of the International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS), and will assume the role of president in 2009.
Dr. Fu, professor and chairman of the department of orthopaedic surgery at the University of Pittsburgh School of Medicine, is the head team physician for the University of Pittsburgh department of athletics. Dr. Fu holds secondary appointments at the university as professor of physical therapy and health physical and recreational education at the School of Health and Rehabilitation Sciences, and at the McGowan Institute.
Dr. Fu is known worldwide for his pioneering surgical techniques to treat sports-related injuries to the knee and shoulder and for his extensive scientific and clinical research in the biomechanics of such injuries. Because of his reputation, Dr. Fu attracts both athletic and non-athletic patients from all over the globe.
ISAKOS was formed in 1999 with the merging of the International Arthroscopy Association and the International Association of the Knee, and has a membership of more than 1,850 orthopaedists from 72 countries. The society serves as an outlet where practitioners can receive the latest information concerning education, research and patient care in arthroscopy, knee surgery and orthopaedic sports medicine. MORE
Samford University in Birmingham Alabama has awarded Alan Meisel, professor of Law and Psychiatry, the Pellegrino Medal “for contributions to American health-care ethics and law.” Professor Meisel is internationally recognized for his work related to end-of-life decision making.
Novel Gene Targeting Products Now Available for Licensing
RheoGene Inc., a biotechnology developer of products and technologies that regulate gene expression, announces the introduction of AttSite™ Recombinases, novel gene-targeting enzymes that direct site-specific DNA modification in a wide range of organisms. Each enzyme catalyzes the irreversible integration or excision of DNA sequences at specific locations within the genome, with broad applications in functional genomics, transgenics technology, biotherapeutic protein production and stem cell and gene therapy.
“AttSite™ Recombinases represent a new generation of gene-targeting tools for life sciences research and product development” said Thomas Tillett, RheoGene CEO. “Each AttSite™ enzyme recognizes a different DNA sequence, therefore different enzyme combinations can be used to reproducibly introduce multiple genes into the same site in the genome, or into different sites in the same cell. Only RheoGene’s AttSite™ platform has this level of precision and flexibility.”
“The ability to precisely control where, when and how alterations are made in the genome has been a significant roadblock to studying gene function and understanding the genetic basis of disease.” said Alan Russell Ph.D., Director of the McGowan Institute and Chairman of RheoGene’s Scientific Advisory Board. “The ability to make targeted genetic modifications at stable, well-characterized loci is critical to advancing the fields of stem cell and gene therapy, where reliability and reproducibility are essential to creating safe and effective therapeutic products for patients with incurable diseases such as cancer, macular degeneration and Parkinson’s Disease.” MORE