What's Happening At The
McGowan Institute?

Mayl 2009 | VOL.8, NO. 5 | www.McGowan.pitt.edu

Successful Hand Transplants Performed

McGowan Faculty Member Dr. W.P. Andrew LeeTeams of surgeons headed by McGowan Institute for Regenerative Medicine faculty member W. P. Andrew Lee, MD, professor of surgery and chief of plastic surgery at the University of Pittsburgh School of Medicine, Division of Plastic and Reconstructive Surgery, have performed a single- and a double-hand transplant on two patients.  Dr. Lee is one of the leading hand surgeons and researchers in the world. 

The first patient, a Marine who was hurt in a training accident, had some movement in his fingers less than 10 days following the single-hand transplant.  He will undergo intense daily physical therapy for 3 months to fully restore movement in his new hand. 

The second patient is a former Air Force member who lost both hands and both feet to a sepsis infection a decade ago.  It took 9 hours and 4 teams of surgeons to perform his double-hand transplant. The patient’s amputations were partway up his forearms, and surgeons attached the donor's hands and lower forearms to his arms after carefully labeling all the tendons, nerves, and muscles that would be attached to each other. 

The transplants were done as part of a study that uses what's called the Pittsburgh Protocol, which has been used in some organ transplants at UPMC.  The Pittsburgh Protocol uses three elements to avoid rejection — treating the patient with antibodies on the day of transplant, performing a donor bone marrow infusion several days later, and using one anti-rejection drug instead of the traditional three.  Some of the side effects of the latter drugs include diabetes and high blood pressure.  “We think we have the potential of accomplishing composite tissue transplants with fewer medications than have been used previously,” Dr. Lee said.

More than 32 patients have received hand transplants worldwide. The first U.S. recipient — who underwent surgery about 10 years ago in Louisville — is the longest surviving hand transplant recipient in the world.  

The UPMC Department of Surgery is one of the leading surgical programs in the country, offering innovative surgical procedures, state-of-the-art technology, and high-quality patient care. Working closely with the Department’s academic partner, the University of Pittsburgh School of Medicine, the department’s surgeons pioneer and refine surgical procedures to provide leading-edge, compassionate care to patients who require surgical services in a wide range of specialties.
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Dr. Borovetz Named Distinguished Professor

McGowan Institute Faculty Member Dr. Harvey Borovetz Harvey Borovetz, PhD, Chair of the Department of Engineering and Robert L. Hardesty Professor in the Department of Surgery at the University of Pittsburgh, and Director of Artificial Organs and Medical Devices at the McGowan Institute for Regenerative Medicine, has been named the Distinguished Professor of Bioengineering.  A distinguished professorship is one of the highest honors given by the University, in recognition of Dr. Borovetz’s highly regarded scholarship, leadership, and contribution to the field of bioengineering.

Dr. Borovetz's research interests are focused on the design and clinical utilization of cardiovascular organ replacements for both adult and pediatric patients.  He has also investigated the role of hemodynamics in vascular biology and physiology.  He is a fellow the American Institute of Medical and Biological Engineering, a past member of the Board of Trustees of the American Society for Artificial Internal Organs, and a past member of the Board of Directors of The Biomedical Engineering Society. He has served on numerous NIH study sections, as an ad hoc reviewer on the Scientific Advisory Committee of the Whitaker Foundation and an external reviewer for the Department of Biomedical Engineering-Rutgers University and the Bioengineering/Biotechnology initiative at the University of Massachusetts.
Congratulations, Dr. Borovetz!
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Welcome to Regenerative Medicine Expert Dr. Tuan

McGowan Faculty Member Dr. Rocky Tuan Rocky S. Tuan, PhD, a world-renowned expert in stem cell biology and tissue engineering, has been appointed the founding director of the University of Pittsburgh School of Medicine’s newly established Center for Cellular and Molecular Engineering in the Department of Orthopaedic Surgery.  For more than 30 years, Dr. Tuan has studied the workings of the musculoskeletal system and its diseases, including cartilage development and repair, cell signaling and matrix biochemistry, stem cell biology, nanotechnology, and many other orthopaedically relevant topics. 

The role of the new Center for Cellular and Molecular Engineering is to develop the knowledge base and the technical know-how toward the restoration of organ functions by applying principles of cellular and molecular biology as well as the physical sciences and engineering. Novel approaches, such as stem cells, biomaterials, nanotechnology, and bioreactors will be utilized to advance skeletal tissue engineering and regeneration.  

“Research has the greatest impact when it is based on real-world needs, developed by means of integrated scientific principles, and delivered using translational approaches,” said Dr. Tuan, who also will serve as the executive vice chairman for orthopaedic research. “My goal is to establish a national and international center of excellence built on research innovation, a strong education program, and an entrepreneurial culture that fosters local and regional collaborations among the academic, industrial, and business communities.”

Since 2001, Dr. Tuan has been chief of the Cartilage Biology and Orthopaedics Branch at the National Institute of Arthritis, and Musculoskeletal and Skin Diseases of the National Institutes of Health. He received his undergraduate education at Swarthmore College and Berea College, and his doctorate in 1977 from Rockefeller University, NY.  Prior to his appointment at NIH, he held professorships in orthopaedic surgery at the University of Pennsylvania and at Thomas Jefferson University, where he also was vice chairman and director of research in the Department of Orthopaedic Surgery. He currently has adjunct appointments at George Washington University School of Medicine and Georgetown University School of Medicine.

Dr. Tuan has served on many professional committees and boards, published significant research papers in top-tier scientific journals, and delivered invited talks at highly regarded academic centers in his field.

Welcome, Dr. Tuan!
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Heart Disease Expert Dr. Cecilia Lo Joins the University of Pittsburgh

University of Pittsburgh faculty member Dr. Cecilia LoCecilia Lo, PhD, a world-renowned expert in research focused on understanding the causes of congenital heart disease, has been appointed the founding chair of the University of Pittsburgh School of Medicine’s newly established Department of Developmental Biology.  A developmental biology department is still uncommon, but very timely and appropriate, noted Arthur S. Levine, MD, dean of the School of Medicine and senior vice chancellor for the health sciences at the University of Pittsburgh.

“Dr. Lo is ideally suited to lead this promising new department,” Dr. Levine said. “Her work is taking significant steps toward discovering the genetic basis for congenital heart disease, and her approach and technologies easily lend themselves to similar analyses for birth defects in other organs.”

In preclinical studies, Dr. Lo has been able to identify novel mutations that cause congenital heart defects such as atrial and ventricular septal defects, transposition of the great arteries, and pulmonary stenosis.

“I am delighted to continue my work at the University of Pittsburgh and look forward to taking on exciting research challenges with my new colleagues in the Pittsburgh’s health sciences community,” Dr. Lo said.

Prior to joining the University’s faculty, Dr. Lo was director of the Genetics and Developmental Biology Center, since 2004, and chief of the Laboratory of Developmental Biology, since 2001, at the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health, Bethesda.  Dr. Lo received her doctorate in 1979 from Rockefeller University and her Bachelor of Science in 1974 from the Massachusetts Institute of Technology, where her advisor was Nobel Laureate David Baltimore. Prior to working at NHLBI, she was a professor of biology in the School of Arts and Sciences at the University of Pennsylvania.

Dr. Lo has served on many professional committees and boards, published significant research papers in top-tier scientific journals, and delivered invited talks at highly regarded academic centers.

Welcome, Dr. Lo!
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Dr. Prashant Kumta Elected Fellow of the American Ceramics Society

McGowan Faculty Member Dr. Prashant KumtaPrashant Kumta, PhD, Edward R. Weidlein Chair at the University of Pittsburgh Swanson School of Engineering and professor in the Departments of BioEngineering, Chemical and Petroleum Engineering, and Mechanical Engineering and Materials Science, has been elected as a fellow of the American Ceramic Society.  Founded in 1898, the American Ceramic Society seeks to serve the informational, educational, and professional needs of the international ceramics community.

Dr. Kumta focuses his research on two broad areas -- energy storage and biomaterials. The primary focus is to develop novel low temperature approaches and study the relationships of the process parameters, the ensuing microstructure and crystallographic structure to the electrochemical activity in the former and biological response in the latter. Fundamental research is also being conducted to explore alternative electronically conductive and electrochemically stable catalyst supports for developing novel electrolyzers for the efficient generation of hydrogen.

Dr. Kumta has been continuously listed in Who’s Who in Science and Engineering and Who’s Who in America, among other prestigious publications.  He is the author and co-author of more than 150 refereed journal publications and is the editor-in-chief of Materials Science and Engineering.

Congratulations, Dr. Kumta!
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Dr. George Michalopoulos Wins Rous-Whipple Award

McGowan faculty member Dr. George Michalopoulos
George Michalopoulos, MD, PhD, Professor and Chairman of the Department of Pathology at the University of Pittsburgh, was presented the 2009 Rous-Whipple Award in Experimental Pathology from the American Society of Investigative Pathology (ASIP).  ASIP serves to promote the discovery, advancement, and dissemination of basic and translational knowledge in experimental pathology and related disciplines.

The ASIP Rous-Whipple Award is granted to a senior scientist with a distinguished career in research, who has advanced the understanding of disease and has continued productivity at the time of this award.

Dr. Michalopoulos is a member of several professional associations and has functioned as consultant with many pharmaceutical and biotechnology companies. He is a co-founder of Kytaron, Inc., a local biotech company working on building small tissues in culture and capitalizing on several new lines of biotechnology.  Dr. Michalopoulos focuses his research on growth factors and receptors in hepatocytes, growth regulation of human hepatocytes, hepatic carcinogenesis, and mechanisms leading to assembly of hepatic tissue.

Congratulations, Dr. Michelopoulos!
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McGowan Institute Faculty Members Named Top-Ranked Physicians

cadeusceusThe McGowan Institute for Regenerative Medicine applauds its clinical faculty members who were recently recognized by Pittsburgh magazine.  Each year the magazine commissions Castle Connolly Medical Ltd. to select top doctors in the region..  The physician-led research team identifies highly skilled, exceptional doctors by evaluating their medical education, training, and hospital appointments, and by surveying area hospital leaders and physicians. 

This year 12 McGowan Institute faculty were recognized in the May issue of the magazine.  Congratulations are extended to:

•          Steven Docimo, MD, Urology
•          Howard Edington, MD, Surgery
•          Freddie Fu, MD, Orthopaedic Surgery
•          Barry Hirsch, MD, Otolaryngology
•          Robert Kormos, MD, Thoracic Surgery
•          W. P. Andrew Lee, MD, Hand Surgery
•          Ernest Manders, MD, Plastic Surgery
•          Michael Pezzone, MD, PhD, Gastroenterology
•          Clark Rosen, MD, Otolaryngology
•          Joel Schuman, MD, Ophthalmology
•          Ron Shapiro, MD, Surgery
•          David Steed, MD, Vascular Surgery

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Depression Drug Study Participants Do Not Reflect Patient Population

McGowan faculty member Dr. Stephen Wisniewski McGowan Institute for Regenerative Medicine faculty member Stephen Wisniewski, PhD, professor of epidemiology and co-director of the Epidemiology Data Center, University of Pittsburgh Graduate School of Public Health, led a team of researchers who reported that findings from clinical studies used to gain Food and Drug Administration approval of common antidepressants are not applicable to most patients with depression.  The study suggests only a small percentage of people with depression qualify for these studies, and those who do not qualify are often treated with the same medications but may suffer poorer clinical outcomes. 

“Results from research studies suggest more optimistic outcomes than may exist for real-world patients receiving treatment for depression,” said Dr. Wisniewski.  Although phase III eligibility criteria could be changed to include a broader population of patients, Dr. Wisniewski cautions that this could come at the cost of more serious side effects in patients who have co-morbidities and are generally sicker. These patients may not be able to safely tolerate the drugs being tested. Instead, he suggests medical care providers who treat patients with depression use their professional judgment by noting that most phase III findings are based on patients who may be very different than those under their care.
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Computer Models Help Illustrate How Neural Networks Function

A real shell (left) and a computer-generated image (right) McGowan Institute for Regenerative Medicine faculty member G. Bard Ermentrout, PhD, University of Pittsburgh Professor of Mathematics and Adjunct Professor of Neurobiology, worked with University of California, Berkeley, scientists on computer models that retrace how mollusks build dazzling shells.  The work illustrates how memory and sensory input influence action.

Dr. Ermentrout, and lead authors, graduate student Alistair Boettiger and Dr. George Oster of Berkeley, modeled the neural network of mollusks and designed a computer program that can generate the complex patterns and shapes of most mollusk shells. The researchers traced the trail of brain activity that begins with a mollusk’s tongue-like organ called a mantle and leads to the cells that produce the shell and pigmentation.

Mr. Boettiger and Drs. Ermentrout and Oster simulated the neural network with integral equations that retrace the previous pattern but can be manipulated to accurately predict how a shell will form under specific conditions. The resulting models help illustrate how neural networks — including mammalian cortices — function in response to a combination of sensory information and experience.
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Dr. William Federspiel Named to NIH Center for Scientific Review

McGowan Faculty Member Dr. William FederspielMcGowan Institute for Regenerative Medicine faculty member William Federspiel, PhD, William Kepler Whiteford Professor of Chemical Engineering, Surgery and Bioengineering, University of Pittsburgh, has been vetted to be a member of the Bioengineering, Technology and Surgical Sciences Study (BTSS) Section of the National Institutes of Health (NIH) Center for Scientific Review (CSR).  The BTSS Study Section reviews grant applications in the interdisciplinary fields of surgery and bioengineering to develop innovative medical instruments, materials, processes, implants, and devices to diagnosis and treat disease and injury. Within BTSS there is a balance between basic, translational, and clinical research, and application and development of emerging cross-cutting technologies relevant to the cardiac system.

CSR is the portal for NIH grant applications and their initial review for scientific merit. CSR organizes the peer review groups or study sections that evaluate the majority (70%) of the research grant applications sent to NIH. CSR’s mission is to see that NIH grant applications receive fair, independent, expert, and timely reviews -- free from inappropriate influences -- so NIH can fund the most promising research.

Congratulations, Dr. Federspiel!

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Human Engineering Research Laboratories

Human Engineering Research Laboratories LogoMcGowan Institute for Regenerative Medicine faculty member Rory Cooper, PhD, leads the staff and mission of the Human Engineering Research Laboratories, or HERL, a partnership between the University of Pittsburgh, the University of Pittsburgh Medical Center, and the Veterans Affairs Pittsburgh Healthcare System.  Now located in about 40,000 square feet in Bakery Square, the former Nabisco plant in Larimer, Pennsylvania, HERL strives to continuously improve the mobility and function of people with disabilities through advanced engineering and medical rehabilitation research.  HERL is one of the worldwide leaders of research and development that increases mobility and function for people with disabilities.

The vast array of research programs of HERL aims to improve a wheelchair user’s independence and quality of life.  One area of interest is in the development of new power wheelchair control devices for people with multiple sclerosis, traumatic brain injury, cerebral palsy, and limited hand strength.  The staff of HERL is also collecting data on the biomechanics of the human body of people who use wheelchairs.  This information will permit the development of better assistive devices and advance safer propulsion and transfer techniques that reduce arm injuries.  HERL has the most comprehensive wheelchair testing laboratory in the U.S., equipped to test manual and power wheelchairs for compliance with International Wheelchair Standards.  The HERL technical staff helped create these standards which dictate the criteria for wheelchair durability and safety.  Another achievement of HERL team members is the invention of the forward folding wheelchair.  This wheelchair model, when compacted, fits in an airplane overhead bin.  It also is designed for use in the very compact aisle inside of an airplane.
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Dr. Rory Cooper Places First in Handcycle Division-Pgh Marathon

McGowan Faculty Member Dr. Rory CooperRory Cooper, PhD, FISA/PVA Endowed Chair and Distinguished Professor of the Department of Rehabilitation Science and Technology, School of Health and Rehabilitation Sciences, University of Pittsburgh, placed first in the handcycle division of the 2009 Pittsburgh Marathon. 

"My original goal was just to finish. To me, it's just for personal goals now, to try to stay healthy and encourage other people to stay healthy," Dr. Cooper said to the Pittsburgh Tribune-Review.

Dr. Cooper completed the marathon with a time of 1:52:48.

Congratulations, Dr. Cooper!
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Regenerative Medicine Podcast Update

The Regenerative Medicine Podcasts remain a popular web destination.  Due to a technical difficulty, many listeners were unable to access the two of the podcasts.  As a result, Regenerative Medicine Today reposted these interviews:
Regenerative Medicine Today

Regenerative Medicine Today #68

Regenerative Medicine Today welcomes Simon Watkins, PhD and Donna Beer Stolz, PhD.  Dr. Watkins is the Founder and Director of the Center for Biologic Imaging at the University of Pittsburgh, and Dr. Stolz is the Associate Director at the Center.  Drs. Watkins and Stolz discuss the many resources available at the Center for Biologic Imaging and the work that is done there.

Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews.

 

Publication of the Month | May 2009
Authors:

Parekh A, Mantle B, Banks J, Swarts JD, Badylak SF, Dohar JE, Hebda PA.

Title:

Repair of the tympanic membrane with urinary bladder matrix.

Summary:

OBJECTIVES: To test urinary bladder matrix (UBM) as a potential treatment for tympanic membrane (TM) healing and regeneration.

STUDY DESIGN: This prospective pilot study was designed to provide both qualitative and semiquantitative assessment of temporal and spatial healing events in the chinchilla model of chronic TM perforations with and without UBM patching.

METHODS: Bilateral myringotomies were performed and repeated as necessary to create subtotal perforations over an 8-week period. Myringoplasty was then performed, with left TMs serving as controls and right TMs receiving UBM patches. TMs were excised at 4 weeks, 8 weeks, and 12 weeks. Fixed tissue samples were characterized for gross morphology, then processed for microscopic evaluation.

RESULTS: Chronic perforations were maintained with one or more repeated myringotomies. Although both control and patched TMs were thicker than native tissue, patched TMs were transparent and uniform in thickness without any inclusions. UBM patches were readily degraded and replaced by newly deposited and organized host tissue that recapitulated the native TM layers.

CONCLUSIONS: UBM scaffolds were an effective biological scaffold for TM closure and tissue remodeling, leading to thicker than normal anatomy but otherwise normal morphology. Future studies are required to determine functional and temporal outcomes as well as alternative patch orientations. The results show particular promise as a superior alternative means of reconstructing not only chronic TM perforations but also dimeric TMs associated with retraction pockets and atelectasis.
Source:

Laryngoscope. 2009 Apr 8;119(6):1206-1213.


Grant of the Month | May 2009

PI

Thomas Gilbert, PhD

Co-Investigators Kimimasa Tobita, MD, PhD and Stephen Badylak, DVM, MD, PhD

Title

Cardiac Remodeling with Organ Specific Extracellular Matrix Scaffolds

Description

Improved materials for cardiac reconstruction of congenital defects and heart failure are needed. Current surgical approaches for cardiac reconstruction utilize synthetic materials that slow the progression of disease, but do not provide any contractile function and do not have the ability to grow with the patient. Recently, porcine urinary bladder matrix (UBM) has been used to repair myocardial tissue. The remodeled UBM contributed to regional function in both canine and porcine models, but did not fully restore myocardial tissue. Cardiac extracellular matrix (C-ECM) may promote faster reconstruction of functional tissue by providing a scaffold with a composition and architecture similar to the tissue that it is intended to replace. The proposed study will determine the morphologic and functional differences in cardiac remodeling after repair with C-ECM, UBM, and Dacron patches. Furthermore, the study will include analysis of the recruitment and fate of bone marrow derived progenitor cells at the site of remodeling.  The study will be conducted in collaboration with Drs. Badylak, Wagner, and Tobita, and members of their respective laboratories.

Source

NIH-NIBIB – RO3

Term

June 1, 2009—May 31, 2011

Amount:

$145,400

Newsletter Comments or Questions: McGowan@pitt.edu