McGowan Institute?
February 2008 | VOL. 7, NO. 2 | www.McGowan.pitt.edu
McGowan Faculty Receive Chancellor’s Research Award!
The Chancellor’s Distinguished Research Award annually recognizes outstanding scholarly accomplishments of members of the University’s faculty who have achieved national and international eminence as an exceptional scholar in their field. This year four faculty in the University of Pittsburgh were recognized in the senior scholar catagory. Three McGowan Institute faculty were amongst these recipients; Stephen Badylak, DVM, PhD, MD, Deputy Director, McGowan Institute, Michael Sacks, PhD, William Kepler Whiteford Professor, Department of Bioengineering, and G. Bard Ermentrout, PhD, University Professor of Computational Biology and Professor-Department of Mathematics. The recipients were honored publicly at the 2008 Honors Convocation on February 29, 2008, as outstanding Senior Scholar Awardees along with other faculty members and students.
As a pioneer in the fields of biomaterials and tissue engineering, Dr. Badylak’s medical advances have been used to treat more than 1.5 million patients throughout the world. Dr. Badylak, Professor, Department of Surgery, was the first to realize that the best biomaterials for tissue regeneration would be those rich in the scaffold matrix proteins found in vivo. These scaffolds, when implanted in the body at the site of a wound, recruit new cells to form tissues identical to the original, injured structures. He also invented new materials that repair and replace damaged human tissues. Importantly, Dr. Badylak’s clinical and medical accomplishments are backed up by solid research studies in highly interdisciplinary areas, such as cell biology, surgery, biochemistry, materials science, tissue engineering, and biomechanics. Dr. Badylak’s peers describe him as “a model for how science, technology, and medicine might be coupled in the 21st century” and “an internationally known researcher in the fields of tissue engineering and biomaterials, a leading authority in the field of transplantations, and a true inventor of important medical products.” As an innovator in his field, “Steve Badylak must be given credit for his pioneering leadership to the biomaterials and tissue engineering community in the area of biological materials…He is considered at the top of his field, truly an international leader.”
Dr. Sacks is a leader in the field of the mechanical behavior of biological and bioprosthetic tissues, who has both developed novel methods to analyze tissue structure and conducted pioneering work in the experimental and theoretical understanding of soft tissue mechanics. Dr. Sacks possesses noted expertise in heart valve analysis and replacement. His use of small angle laser scattering to analyze the collagen substructure in heart valve and tissue-derived replacements provides a critically valuable window into the structural basis for valve mechanics. Scientific American named Dr. Sacks as one of its top 50 researchers for 2006 for his seminal work on the biomechanics of biological scaffolds for cardiac regeneration. Dr. Sacks’ peers describe him as “a leading investigator in the solid mechanics and functional fibrous architecture of heart valves and other collagenous tissues,” whose “contributions to the understanding of prosthetic heart valve leaflet biomechanics and heart failure mechanisms have been exceedingly helpful…” “Dr. Sacks is considered a world class leader in tissue mechanics, highly recognized, and constantly accelerating his research activity” and “…has established himself as the world leader in heart valve tissue mechanics…”
Dr. Ermentrout not only possesses an international reputation in mathematical modeling, but is renowned across several disciplines. He is considered to be among the world’s top researchers in the field of computational neuroscience. “There are few fields that your work on mathematical modeling has not touched, and in so doing, made a lasting impact. You are highly sought after for your unique insights and contributions to the modeling of neural and biological systems, ranging from the brain, neurons, and cognition to viruses and olfaction,” Chancellor Nordenberg wrote. Ermentrout’s work in such leading scientific journals as the Proceedings of the National Academy of Sciences, Nature, and Science has been cited by other researchers more than 135 times per year on the average, with each of his publications receiving an average of more than 27 citations. Ermentrout’s colleagues, in letters supporting his nomination, described him as “a genius, an outstanding scholar, and a prolific contributor to several disciplines” who has garnered both national and international recognition and respect for his contributions.
Congratulations, Drs. Badylak, Sacks and Ermentrout! Read More...
CBS Evening News highlighted the work of several McGowan Institute researchers and characterized these pioneering studies as the “Holy Grail of Healing” of regenerative medicine. The innovative work of McGowan Institute researchers—Drs. Stephen Badylak, Jorge Gerlach, William Wagner, and Joon Sup Lee—was featured in the coverage.
Read more and get links to the CBS Video...
Over 225 faculty, trainees and guests are planning to attend the Seventh Annual McGowan Institute scientific retreat on March 10, 11, and 12 at Nemacolin Woodlands. Guest speakers include a vast array of preeminent scientists, led by Dr. Irving Weissman, who will deliver the McGowan Distinguished Lecture. Other distinguished leaders include Elizabeth Roberts, Lieutenant Governor of Rhode Island and Rebecca Bagley, Deputy Secretary for Technology Investment for the Department of Community and Economic Development. Lieutenant Governor Roberts was instrumental in Rhode Island’s push towards stem cell and regenerative medicine research and commercial ventures.
Registration for the Retreat is closed, but look for Retreat updates in the March newsletter.
The Pittsburgh Intellectual Property Law Association (PIPLA) has selected Dr. Stephan Badylak as its 2008 Inventor of the Year. The PIPLA Inventor of the Year Award is awarded annually to honor inventors whose patented inventions have a significant impact on the economy, the social well being, and the advancement of technology. Dr. Badylak received a plaque recognizing his accomplishments at a recent dinner meeting of the Association in downtown Pittsburgh.
Dr. Badylak’s intellectual property is primarily based on his identification that a strong yet pliable tissue harvested from porcine small intestine provides an inductive scaffold for host cells to replace and constructively remodel damaged or missing tissue. This biomaterial is called small intestinal submucosa, or SIS, and it is a naturally-occurring, complex matrix that is easy to handle, yet strong enough to hold sutures and provide support for weakened tissue.
As a naturally-derived extracellular matrix (ECM) material, SIS is composed of structural and functional molecules maintained in their native 3-dimensional ultrastructure. SIS is not chemically cross-linked. Since SIS is taken from a biological source and is processed to remove all cells, it is biocompatible and safe for human use. It is sterilized to eliminate pathogens and has a shelf life measured in years instead of months.
The licensing rights to subsets of Dr. Badylak’s patent portfolio have been licensed to five separate entities beginning as early as 1988.
More than 60 separate medical device products are now commercially available as a result of this patent portfolio. These products provide therapeutic value in many medical fields including topical wound care, lower urinary tract reconstruction, cardiovascular tissue repair and reconstruction, central nervous system repair and reconstruction, gastrointestinal tract remodeling, and the treatment of endocrine diseases such as Type I diabetes. More than 1.5 million patients worldwide have been helped by this technology, clearly making it the most successful and widely utilized tissue engineered material that has ever reached clinical practice.
Six-year-old Seth Breese has a smile that could melt your heart. And speaking of hearts, Seth has a brand new one, transplanted in September by Dr. Peter Wearden of Children’s Hospital of Pittsburgh of UPMC and due to the generosity of a donor family.
Seth’s story actually begins when he was diagnosed soon after birth with dilated cardiomyopathy—a condition in which the heart is weakened and enlarged and cannot pump blood efficiently. Last summer Seth began to feel lethargic and was unable to eat and do other normal activities. He was brought to Children’s Hospital and listed on the transplant list in mid-August.
Because of the fact that Seth’s condition was deteriorating and the heart output was low, he first underwent surgery to place a VAD (ventricular assist device) called the Centrimag Blood Pumping System, manufactured by Levitronix, LLC.
The reason that Seth’s case is making medical news is that although the Centrimag device has been used before, and is FDA approved in adults as a blood pumping system, this is one of the first times it has been used as a VAD on a child in the United States and the first time it has ever been used at Children’s Hospital of Pittsburgh.
Much of the preclinical testing of this VAD was done by researchers and faculty at the McGowan Institute for Regenerative Medicine including Harvey Borovetz, PhD and the surgeon in charge of Seth’s case, Peter Wearden, MD, an assistant professor in Pediatric Cardiac Surgery and Director of Pediatric Mechanical Cardiopulmonary Support at Children’s. Dr. Kurt Dasse of Levitronix was the developer and designer of the device.
Dr. Borovetz has made the development of a pediatric VAD one of his personal and professional goals. In discussing the history of these cardiac support devices he states, “The first ECMO [utilization] for cardiac support in an infant was performed in 1977. Thirty years later, exciting new technology is becoming available for these patients, and the McGowan Institute for Regenerative Medicine’s participation is helping to make this possible.” Listen to Dr. Borovetz’s Regenerative Medicine Podcast on the development of circulatory support devices.
The Centrimag is a continuous-flow, centrifugal-type rotary blood pump that is placed outside the body. The pump housing and rotor are made of medical-grade polycarbonate, designed for single-use. The centrifugal pump design permits rotation of the impeller (the only moving part inside the pump) at lower speeds, while still achieving desired flow rates. The Centrimag causes very little damage to the blood because it does not contain any bearings or seals—components that are known to cause destruction of red blood cells and promote blood clot formation.
McGowan and Children’s researchers will continue their efforts to develop a pediatric VAD. Seth’s case was a special one that permitted the use of the adult Centrimag on a child, but there are various other clinical trials currently underway at the Children’s Heart Center to provide improved protocols and better methods of sustaining circulation during cardiorespiratory decompensation in infants and children.
These days, Seth is once more enjoying his life as a six-year-old. According to his parents, Kim and Jarrod of Greenville, Mercer County, Seth’s favorite activities include playing video games, watching TV, and like a typical little brother, irritating his sister, McKenna, age eight. With the reappearance of Seth’s smile over the last few months, there is no question that Valentine’s Day at the Breese household this year will take on a whole new meaning.
McGowan Institute for Regenerative Medicine faculty member Hans-Christoph Pape, MD, Associate Professor of Orthopaedic Surgery and Chief of the Division of Orthopaedic Traumatology at the University of Pittsburgh School of Medicine and UPMC, recently reported at the 23rd Annual Meeting of the Orthopaedic Trauma Association in Boston that polytrauma patients who are in an uncertain condition and receive initial external fixation for femoral shaft fractures have a significantly lower incidence of lung dysfunction than those undergoing intramedullary femoral nailing. The prospective, multicenter study, which began enrolling participants in 1999, was aimed at addressing the need for more definitive data regarding the benefits of initial temporary fixation of femoral shaft fractures in trauma patients. The Orthopaedic Trauma Association identified Dr. Pape’s paper as a Winning Highlight Paper.
Read more...
McGowan Institute scientists Brack G. Hattler, MD, PhD (bottom), and William J. Federspiel, PhD (top) currently are conducting laboratory studies that are tackling fundamental problems associated with making artificial lungs more efficient and biocompatible, and are developing next generation artificial lungs or blood oxygenators.
The purpose of an artificial lung is to help lung-failure patients survive the tenuous bridge of time between loss of respiratory function and a lung transplant, and to allow a patient whose lungs have undergone trauma, like severe smoke inhalation, to rest and heal. Artificial lungs are small and portable, and are designed to allow patients to remain mobile and therefore stronger for surgery. In healthy lungs, blood vessels absorb oxygen from the blood that's pumped in from the heart, then release carbon dioxide through exhalation. An artificial lung basically imitates the way a normal lung works.
Researchers in Pittsburgh who are developing and testing prototypes believe artificial lung clinical trials in humans, similar to studies already underway in Canada and Europe, may begin as early as this spring. Read more…
The Pittsburgh Business Times recently interviewed Alan Russell, PhD, Director, McGowan Institute for Regenerative Medicine. In its column, “Five Minutes With,” Dr. Russell responded to several questions posed to him about today’s therapies that reestablish tissue and organ function. Dr. Russell’s efforts have helped propel Pittsburgh and the Southwestern Pennsylvania region to preeminence in tissue engineering through his continued support of university-based research and education, and by pairing tissue engineering scientists with technology transfer opportunities to help them build our regional biotechnology enterprise. Read more…
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The Regenerative Medicine Podcasts continue to explore pertinent topics. The most recent podcasts are:
#48-Joan Schanck – Ms. Schanck visits Regenerative Medicine Today and discusses the PTEI programs on education and public awareness related to tissue engineering and regenerative medicine.
#47-Dr. Phil Campbell - Dr. Campbell discusses his research that is focused on the development of “tool sets” that will be resources for regenerative medicine research and clinical therapies. In the podcast he discusses his work on methodologies and systems that will be required for cell expansion on a commercial vs. a research basis, and how his research is addressing those needs. He also shares some insight into his strong commitment to science-based education: from elementary students to senior citizens.
Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews.
| Authors: | Koji Tomiyama, Noriko Murase, Donna Beer Stolz, Hideyoshi Toyokawa, Daniel R. O'Donnell, Darren M. Smith, Jason R. Dudas, J. Peter Rubin and Kacey G. Marra |
| Title: | Characterization of Transplanted Green Fluorescent Protein+ Bone Marrow Cells into Adipose Tissue |
| Summary: | Following transplantation of green fluorescent protein (GFP)-labeled bone marrow (BM) into irradiated, wild-type Sprague-Dawley rats, propagated GFP_ cells migrate to adipose tissue compartments. To determine the relationship between GFP_ BM-derived cells and tissue-resident GFP_cells on the stem cell population of adipose tissue, we conducted detailed immunohistochemical analysis of chimeric whole fat compartments and subsequently isolated and characterized adipose-derived stem cells (ASCs) from GFP_BM chimeras. In immunohistochemistry, a large fraction of GFP_ cells in adipose tissue were strongly positive for CD45 and smooth muscle actin and were evenly scattered around the adipocytes and blood vessels, whereas all CD45_ cells within the blood vessels were GFP_. A small fraction of GFP_ cells with the mesenchymal marker CD90 also existed in the perivascular area. Flow cytometric and immunocytochemical analyses showed that cultured ASCs were CD45_/CD90_/CD29_. There was a significant difference in both the cell number and phenotype of the GFP_ ASCs in two different adipose compartments, the omental (abdominal) and the inguinal (subcutaneous) fat pads; a significantly higher number of GFP_/CD90_ cells were isolated from the subcutaneous depot as compared with the abdominal depot. The in vitro adipogenic differentiation of the ASCs was achieved; however, all cells that had differentiated were GFP. Based on phenotypical analysis, GFP_ cells in adipose tissue in this rat model appear to be of both hematopoietic and mesenchymal origin; however, infrequent isolation of GFP_ ASCs and their lack of adipogenic differentiation suggest that the contribution of BM to ASC generation might be minor. |
| Source: | Stem Cells 2008;26;330-338; originally published online Nov 1, 2007; DOI: 10.1634/stemcells. 2007-0567 |
| PIs: | Drs. Badylak and Gerlach |
| Title: | Advanced Regenerative Medicine (ARM) Therapies for Combat Injuries |
| Description: | Badylak: Digit regeneration using porcine derived scaffolds Gerlach: Wound cap for tissue regeneration Gerlach: Skin gun for burn therapy |
| Source: | Pittsburgh Tissue Engineering Initiative, Inc |
| Term: | 11/01/07 – 10/31/08 |
| Amount: | $1,005,762 |
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