McGowan Institute?
April 2009 | VOL.8, NO. 4 | www.McGowan.pitt.edu
Corneal Therapies May Treat Human Blindness/Vision Impairment
McGowan Institute for Regenerative Medicine faculty member James L. Funderburgh, PhD, associate professor, Department of Ophthalmology, University of Pittsburgh School of Medicine, led a research team which recently reported that stem cells collected from human corneas restore transparency and don’t trigger a rejection response when injected into eyes that are scarred and hazy, according to their experiments conducted in mice. The findings suggest that cell-based therapies might be an effective way to treat human corneal blindness and vision impairment due to the scarring that occurs after infection, trauma, and other common eye problems, said Dr. Funderburgh. The corneal stem cells were able to remodel scar-like tissue back to normal.
“Our experiments indicate that after stem cell treatment, mouse eyes that initially had corneal defects looked no different than mouse eyes that had never been damaged,” Dr. Funderburgh said.
The ability to grow millions of the cells in the lab could make it possible to create an off-the-shelf product, which would be especially useful in countries that have limited medical and surgical resources but a great burden of eye disease due to infections and trauma.
“Corneal scars are permanent, so the best available solution is corneal transplant,” Dr. Funderburgh said. “Transplants have a high success rate, but they don’t last forever. The current popularity of LASIK corrective eye surgery is expected to substantially reduce the availability of donor tissue because the procedure alters the cornea in a way that makes it unsuitable for transplantation.”
In the next steps, the researchers intend to use the stem cells to treat lab animals that have corneal scars to see if they, too, can be repaired with stem cells. Under the auspices of UPMC Eye Center’s recently established Center for Vision Restoration, they plan also to develop the necessary protocols to enable clinical testing of the cells.
The Oprah Show recently featured the science and technology of today’s regenerative medicine efforts on its show entitled, “High-Tech Ways to Extend Your Life.” In one segment, audiences were introduced to extracellular matrix, or ECM, and how it heals the body. The use of ECM for the repair of soft tissues was pioneered by Stephen Badylak, DVM, PhD, MD, Deputy Director of the McGowan Institute, Director of the Pre-Clinical Studies Center at the McGowan Institute, and Research Professor in the University of Pittsburgh’s Department of Surgery. Dr. Badylak’s ECM technologies have permitted others to offer innovative solutions to unique and challenging tissue regeneration needs.
In the 1980s, Dr. Badylak identified the importance of ECM, which harbors signaling molecules that help direct the development of cells into tissue, during a preclinical experiment in which he used a portion of an intestine to fashion a makeshift aorta for a heart. Not only was the surgery successful, but months later, an examination revealed that the transplanted intestine part had morphed into a vessel that looked much like an aorta. There was hardly any scarring.
Subsequent research has helped Dr. Badylak and his colleagues understand the mechanisms behind this remarkable tissue remodeling. That research used a layer of intestinal lining called the submucosa, a form of a biological scaffold to support new tissue growth. Dr. Badylak's team found that extracting the submucosa from the intestine and putting patches of it at injury sites triggered a novel healing response: as the implanted matrix material broke down, healthy living tissue - not scar tissue - repaired the damage.
Featured on Oprah was the story of a 70-year-old hobby shop owner, Lee Spievack, who accidentally lopped off about three-eighths of an inch off the top of his middle finger on the propeller of a model airplane. A novel treatment was devised by Spievack’s brother, using ECM technology that was based on the Badylak concept. The powdered form of ECM was applied to the end of the severed finger every other day for 10 days; in 4 weeks, the wound was healed. In 4 months the finger resembled the original finger prior to the accident.
Today, Dr. Badylak’s laboratory is a highly interdisciplinary environment. The major focus of the laboratory is the development of regenerative medicine strategies for tissue and organ replacement. The use of mammalian ECM or its derivatives as an inductive template for constructive remodeling of tissue is a common theme of most research activities in the Badylak Lab. The goal of all projects is clinical translation and improved patient care.
The research efforts of several McGowan Institute faculty members and their laboratories were the recent topics of discussion on HealthRadio.Net. William Wagner, PhD, Deputy Director, McGowan Institute, Professor of Surgery, Bioengineering and Chemical Engineering at the University of Pittsburgh, as well as the Director of Thrombosis Research for the Artificial Heart and Lung Program, was interviewed by the HealthRadio.Net show’s host, Derrick M. DeSilva, Jr., M.D. Dr. DeSilva is a practicing Internist and part of the Attending Staff at the Raritan Bay Medical Center, Perth Amboy, NJ. Their conversation included topics relative to what is regenerative medicine, the use of biomaterials to assist in the repair of the body, and new approaches for the treatment of cardiovascular disease.
Dr. Wagner broadly defines regenerative medicine during the show as such: “Regenerative medicine is harnessing or engineering the body’s natural ability to heal.” At the McGowan Institute, he explained, research is focused on three major regenerative medicine categories: cell therapy, tissue engineering and biomaterials, and medical devices. The research of the McGowan Institute involves “the marriage of engineering and medicine,” as described by Dr. Wagner. During the broadcasts, the discussion with Dr. DeSilva also touched on ventricular assist devices, blood vessel repair materials, heart stents, metallic biomaterials that safely corrode in the body and facility healing, neonate (pediatric) blood pumps, repair and remodeling of heart arteries through cell therapy, organ and limb regeneration with extracellular matrix, adult- vs. embryonic-derived stem cells, and new blood vessel growth.
HealthRadio.Net is a free online Health News & Information Source providing live, interactive Talk Shows about Health - interviewing over 50 expert medical and health guests each week. HealthRadio.Net is also an audio content provider distributing its audio and Podcast interviews to third party Websites. HealthRadio has built a steady user base of listeners due to positive word-of-mouth with some 200 expert guests per month informing their constituencies about the interviews, high listings on search engines, external links to its site, and favorable media attention.
You can listen to Dr. Wagner’s interview on HealthRadio.Net here…
McGowan Institute for Regenerative Medicine faculty member Joel Schuman, MD, Eye and Ear Foundation Professor and chairman of Ophthalmology, director of the UPMC Eye Center, and University of Pittsburgh professor in Bioengineering, helped create ultra-detailed, 3 dimensional (3-D) images of the eyes of more than 2,000 people from different ethnic groups. Four hundred of these patients have age-related macular degeneration (AMD), which is the leading cause of vision loss in Americans and Europeans over 50. This work gave scientists a better look at the abnormalities that cause AMD. Results of the study’s research groups of James Fujimoto at the Massachusetts Institute of Technology and collaborators Jay Duker of the Tufts University School of Medicine and Dr. Schuman may pave the way for new diagnostic software useful for developing new treatments.
AMD is a condition in which the macula -- the region of highest visual acuity in the retina -- stops functioning properly. AMD causes blurred vision and, in advanced cases, a large blind spot in the center of one’s vision.
Optical coherence tomography (OCT) has become a standard tool for assessing AMD and other eye diseases. An OCT instrument shoots beams of infrared light into the retina, where they are reflected to greater or lesser extent by different structures within the eye. By measuring the echo time delays of reflected light, an ophthalmologist can have a cross-sectional or 3 D view of the retina’s layers. This high resolution, 3-D image reveals abnormalities that can be used to track disease progression and response to treatment.
The team used an OCT machine with a resolution two times higher than commercial OCTs. In this study, they imaged the retinas of 400 people suffering from different stages of macular degeneration. Their profiles range from a 54-year-old man with mild AMD and 20/20 vision, to a 77-year-old woman with advanced AMD who can just barely count fingers from a distance of 4 feet. Each person's eye was scanned in 180 different slices and stitched together to form a 3-D image of the eye.
The research team published the electronic data in these 3-D images in order to make it available to the image processing community to develop computer programs that can quickly and automatically detect the details and severity of the disease -- by counting the number of drusens, for example, or quantifying the volume of fluid leaked into the eye by faulty blood vessels. Developing these programs will be difficult because of the sheer quantity of data contained in each data set, but it is important because quantitative measurements can be used to track disease progression and help establish correlations between the severity of vision loss and changes in the architecture of the eye.
This could provide a faster and more efficient way for drug makers to develop and evaluate new treatments in clinical trials. No treatment currently exists for dry AMD, and treatments for the wet form -- including lasers that burn the blood vessels and drugs that inhibit the growth of new vessels -- can only slow, not stop, vision loss.
McGowan Institute for Regenerative Medicine faculty member Tim Oury, MD, PhD, Associate Professor, Department of Pathology at the University of Pittsburgh, and member of the Simmons Center for Interstitial Lung Disease at the University of Pittsburgh Medical Center, was part of a team of U.S. and German scientists who recently reported that mutations in a gene may cause poor lung development in children, making them more vulnerable to diseases such as chronic obstructive pulmonary disease (COPD) later in life. Their study measured expression levels of the gene and its variants in both mouse lungs and children ages 9 to 11.
Dr. Oury, along with study authors led by George Leikauf, Ph.D., professor of occupational and environmental health at the University of Pittsburgh Graduate School of Public Health, and Holger Schulz, M.D., professor of medicine at the Institute of Lung Biology and Disease, German Research Center for Environmental Health, Munich, focused on a gene called superoxide dismutase 3 (SOD3), previously shown to protect the lungs from the effects of asbestos and oxidative stress.
The team of researchers compared SOD3 expression levels in strains of mice with poor lung function to one with more efficient airways and lungs two times the size. As with people, the lungs of mice fully form as they mature to adulthood. The better-functioning strain maintained higher levels of SOD3 – levels in these mice were four times higher at the final stage of lung development. They also found the presence of single nucleotide polymorphisms, or SNPs, variations in DNA sequences, in SOD3 that were linked to lung function in mice.
The researchers went on to assess SOD3 mutations in children ages 9 to 11 by testing for SNPs linked to lung function. After analyzing DNA from 1,555 children in Munich and Dresden who were part of the International Study of Asthma and Allergy in Children, they discovered two common SNPs associated with poorer lung function. One of these SNPs likely alters the expression levels of SOD3. Lung function was tested with spirometry, which measures the amount and speed of exhaled air.
Previously, genetic variants in SOD3 have been associated with loss of lung function in COPD, which is mainly caused by cigarette smoking. SOD3 protects the lung against injury caused by the chemicals in cigarette smoke. The gene variant could be a link between childhood exposure to environmental tobacco smoke and poor lung development. In the future it might be possible to identify at-risk children and to develop a medication that would foster optimal lung development. The researchers also are exploring sex differences in SOD3 gene expression and lung development, and girls appear to be at greater risk than boys.
COPD is the fourth leading cause of death in the United States, accounting for more than 120,000 deaths annually and costing more than $30 billion per year. It is estimated that more than 16 million Americans have COPD.
McGowan Institute for Regenerative Medicine faculty member Michael Sacks, PhD, professor of bioengineering at the University of Pittsburgh and Director of the Engineered Tissue Mechanics and Mechanobiology Laboratory, was named the first John A. Swanson Endowed Chair in recognition of his outstanding research accomplishments and service to the bioengineering community, both nationally and internationally. According to Provost James V. Maher, this is “the highest honors accorded to a member of the professorate.” As Swanson Chair, Dr. Sacks will continue to be a major contributor to the research and educational mission of the Department of Bioengineering and the Swanson School of Engineering.
Dr. Sacks focuses his research on the quantification and modeling of the structure-mechanical properties of native and engineered soft tissues, with an emphasis on the tissues of the cardiovascular and urological systems. In particular, his laboratory has focused on the mechanical behavior and function of the native aortic and mitral heart valves, including the development of the first constitutive (stress-strain) models for these tissues using a structural approach. His laboratory is also active in the biomechanics of engineered tissues and in understanding the in-vitro and in-vivo remodeling processes from a functional biomechanical perspective.
Earlier this year, Sacks received the Van C. Mow Medal from the American Society of Mechanical Engineers (ASME) for his contributions in advancing biomechanics of native and engineered heart valve tissues.
Congratulations, Dr. Sacks!
Read more. . .
McGowan Institute for Regenerative Medicine faculty members David J. Hackam, MD, PhD (top), Department of Pediatric Surgery, and Satdarshan P.S. Monga, MD (bottom), Department of Pathology, were elected into the American Society for Clinical Investigation (ASCI). This honor recognizes the contributions of physician-scientists at a young age. They were officially inducted into the Society at the ASCI/AAP Joint Meeting in Chicago.
The ASCI, established in 1908, is one of the nation's oldest and most respected medical honor societies. The ASCI comprises more than 2,800 physician-scientists from all medical specialties elected to the Society for their outstanding records of scholarly achievement in biomedical research. The ASCI is dedicated to the advancement of research that extends our understanding and improves the treatment of human diseases, and members are committed to mentoring future generations of physician-scientists. The ASCI considers the nominations of several hundred physician-scientists from the United States and abroad each year and elects up to 80 new members each year for their significant research accomplishments. Because members must be 45 years of age or younger at the time of their election, membership reflects accomplishments by its members relatively early in their careers.
Dr. David Hackam is currently the Roberta Simmons Associate Professor of Surgery and Associate Professor of Cell Biology and Physiology at the University of Pittsburgh School of Medicine. He is also an Attending Surgeon a Children’s Hospital of Pittsburgh of UPMC. Dr. Hackam teaches Pediatric Surgery Education Sessions for Medical Students at Children’s Hospital, is involved in the Student Shadow Program also at Children’s Hospital, assists in the Student Research Summer Training Program at the University of Pittsburgh, and is also involved in the Student Research Summer Training Program at Children’s. Dr. Hackam is currently the Director of the Surgical Translational Research Training Program Department of Surgery, University of Pittsburgh, and is the Co-Director of the Fetal Diagnosis and Treatment Center Magee-Womens Hospital of UPMC in partnership with Children’s Hospital. Dr. Hackam's current research interests include exploring novel therapeutic targets for treating conditions of intestinal inflamation, such as necrotizing entercolitis, Crohn's disease, and infection. He also is working to better understand the mechanisms of phagocytosis of pathogens by macrophages in neonates during conditions of inflammation.
Dr. Satdarshan “Paul” Monga is an Associate Professor of Pathology and Medicine at the University of Pittsburgh School of Medicine. Additionally, he is an Assistant Professor of Gastrointestinal Oncology at the University of Pittsburgh Cancer Institute and an active member of the liver section at the McGowan Institute. Dr. Monga's primary research efforts include hepatic stem cell characterization, culture, and transplantation including intra-uterine techniques; Wnt/b-catenin signaling pathway in liver utilizing a liver regeneration model, primary hepatocyte cultures, embryonic liver development, and transgenic models, and identifying novel targets of this pathway with emphasis on role in liver development and carcinogenesis; cross talk between prominent signal transduction pathways, especially Wnt, HGF, and TGF, identifying novel targets and elucidating interactions during development, growth, and carcinogenesis; and, studying carcinogenesis and utilizing novel approaches to identify cancer progenitor cells in the liver and gut, and applying antisense technology to study carcinogenesis and a possible therapeutic role.
The laboratory website of McGowan Institute for Regenerative Medicine faculty member Steven Little, PhD, Assistant Professor and Bicentennial Alumni Faculty Fellow, University of Pittsburgh Departments of Chemical Engineering, Bioengineering, and Immunology, recently received the honor of being named the “most creative flash website in the Pittsburgh area.” During the 2009 Pittsburgh ADDY Award Show held at the Carnegie Museum, the site’s developer, Wall-to-Wall Studios, accepted the Gold Award for its original and artistic efforts in representing the innovation and creative excellence that the researchers of Dr. Little’s lab put into each idea and into each experiment.
The Pittsburgh ADDY Awards Competition is the first of a three-tiered national competition conducted annually by the American Advertising Federation (AAF). The ADDY Awards Competition is the industry's largest and most representative competition for creative excellence. It is the only creative awards program administered by the advertising industry for the industry.
The Pittsburgh ADDY Awards program is an opportunity to acknowledge the creative efforts of the Pittsburgh AAF peers and colleagues.
The Pittsburgh Advertising Federation is an organization with over 250 professionals involved in all aspects of advertising, marketing, and public relations.
The Pittsburgh Advertising Federation strives to encourage and nurture integrity and excellence in advertising as well as assisting each other through many resources. The Pittsburgh Advertising Federation is a member of the AAF, which is a national organization, empowered by 50,000 professionals in 220 professional advertising clubs, 220 college chapters, and 110 corporations. The Pittsburgh Advertising Federation meets it members' needs through networking and educational opportunities, while celebrating the talent of Pittsburgh's advertising achievements with extraordinary energy and passion. The Pittsburgh Advertising Federation was founded in 1923.
Congratulations, Dr. Little!
McGowan Institute for Regenerative Medicine faculty member Freddie H. Fu, MD, renowned UPMC (University of Pittsburgh Medical Center) orthopaedic surgeon, was named president of the prestigious International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine (ISAKOS) at its Biennial Congress in Osaka, Japan. Dr. Fu, who has been a member of the ISAKOS Board of Directors for 10 years, will serve a 2-year term as president.
“My mission over the next 2 years as ISAKOS president is to integrate international leaders to provide education, research experience, and opportunities via meetings and mentorship for ISAKOS members, especially in countries where technologies are being developed,” said Dr. Fu. “The society will partner with regional societies to enhance our missions, and work with industry leaders, as well as to provide educational and research opportunities for ISAKOS members.”
ISAKOS is considered the preeminent international forum for the exchange of ideas that advance arthroscopy, knee surgery, and orthopaedic sports medicine. ISAKOS promotes and provides educational opportunities for specialists from every corner of the globe, across cultural traditions and economic disparities, including developing countries. This year’s Congress has brought together world leaders from more than 75 countries to experience unique diversity and education through instructional course lectures, scientific papers, philosophical debates, symposia, lectures, and hands-on workshops.
Dr. Fu has been the David Silver Professor and Chair of the Department of Orthopaedic Surgery at the University of Pittsburgh School of Medicine since 1997. He was the founding medical director of UPMC’s Center for Sports Medicine, regarded as one of the country’s top sports medicine research and clinical programs. And, under his chairmanship, the UPMC Department of Orthopaedic Surgery currently is ranked among the top 10 in the U.S. News & World Report annual Best Hospitals survey.
Dr. Fu also is the current president of the American Orthopaedic Society for Sports Medicine (AOSSM). He is world-renowned as a pioneer in numerous innovative arthroscopic surgical techniques to treat injuries to the knee and shoulder. He also is heralded for his extensive research in biomechanics, in vivo kinematics, comparative anatomy, stem cell, and regenerative medicine involving the knee.
The Joseph M. Katz Graduate School of Business MBA curriculum includes a project course that is designed to provide MBA students a meaningful and measurable business experience prior to graduation. These projects offer the opportunity for students to apply the various analytical tools and concepts learned at Katz while providing valuable and practical project assistance to participating businesses.
The projects range over many academic disciplines. In performing their work, the teams are supported by a faculty advisor as well as consulting workshops led by McKinsey and Company, management consultants. Key to the course is the guidance and critique provided by the participating client organizations and the Katz faculty.
During the Spring 2009 semester, there were 17 Katz project teams that worked with clients. One of those teams worked with the McGowan Institute assessing the commercial opportunities for an emerging McGowan Institute Technology-AngioShield, which is a biodegradable sheath that has been designed to help the transition of the traditional saphenous vein graft to an arterial vein replacement in the bypass procedure. Despite the extensive use of saphenous veins, the failure of arterial vein grafts (AVGs) is a major problem; 12-27% of AVGs become occluded in the first year with a subsequent annual occlusive rate of 2-4%. Failed AVGs cause increased morbidity or require re-operation.
With the AngioShield sheath, clinicians will be able achieve superior outcomes for treatment of coronary and peripheral arterial re-vascularization. The overall result is expected to be reduced AVG failure rates, and subsequently less money spent in the treatment of chronic patients.
The McKinsey Cup Competition is culmination of the project courses and seeks to recognize the contributions of the project teams, and to identify the most successful projects. Four semifinalist teams were selected to participate in the prestigious McKinsey Cup Competition, where each team presents their project to a panel of judges as well as an audience of judges with electronic voting devices.
The McGowan Team was selected to participate in the McKinsey Cup competition and was then selected as the first place winner of the McKinsey Cup. The Team members are Khaleel Khaja, Patrick McIlwain, Daniel O'Donnell, and Matthew Stevenson.
The Katz faculty advisors were William Hoos, Rabikar Chatterjee, PhD, and G.M. (Bud) Smith Jr. served as the overall project course coordinator.
McGowan Institute leadership included Patrick Cantini, Lorenzo Soletti, PhD and Mohammed El-Kurdi, PhD.
The Institute extends our appreciation to the Team and to the Joseph M. Katz Graduate School of Business faculty for their superb contributions on the assessment and recommendations for the commercialization of this McGowan Institute developed technology.
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:
#67 – Eric Beckman, PhD – Dr. Beckman is a professor of chemical engineering at the University of Pittsburgh and the co-founder of Cohera Medical, Inc. Dr. Beckman discusses the technology that is being developed at Cohera Medical, Inc. as well as the difficulties faced when starting a small company.
Visit www.regenerativemedicinetoday.com to keep abreast of the new interviews.
| Authors: |
Rothstein SN, Federspiel WJ, Little SR. |
| Title: | A unified mathematical model for the prediction of controlled release from surface and bulk eroding polymer matrices. |
| Summary: | A unified model has been developed to predict release not only from bulk eroding and surface eroding systems but also from matrices that transition from surface eroding to bulk eroding behavior during the course of degradation. This broad applicability is afforded by fundamental diffusion/reaction equations that can describe a wide variety of scenarios including hydration of and mass loss from a hydrolysable polymer matrix. Together, these equations naturally account for spatial distributions of polymer degradation rate. In this model paradigm, the theoretical minimal size required for a matrix to exhibit degradation under surface eroding conditions was calculated for various polymer types and then verified by empirical data from the literature. An additional set of equations accounts for dissolution- and/or degradation-based release, which are dependent upon hydration of the matrix and erosion of the polymer. To test the model's accuracy, predictions for agent egress were compared to experimental data from polyanhydride and polyorthoester implants that were postulated to undergo either dissolution-limited or degradation-controlled release. Because these predictions are calculated solely from readily attainable design parameters, it seems likely that this model could be used to guide the design controlled release formulations that produce a broad array of custom release profiles. |
| Source: | Biomaterials. 2009 Mar;30(8):1657-64. Epub 2008 Dec 19. |
PI |
Johnny Huard |
Title |
Tissue Engineered Skeletal Muscle (TESM) from Muscle Progenitor Cells: A Model for Studying Insulin Resistance and Muscle Metabolism |
Description |
The overall specific aims are as follows:
|
Source |
Pfizer |
Term |
March 1, 2009 – February 28, 2011 |
| Amount: | $475,000 |
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