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Regenerative medicine approach improves muscle strength, function in leg injuries

2014-04-30
(Press-News.org) PITTSBURGH, April 30, 2014 – Damaged leg muscles grew stronger and showed signs of regeneration in three out of five men whose old injuries were surgically implanted with extracellular matrix (ECM) derived from pig bladder, according to a new study conducted by researchers at the University of Pittsburgh School of Medicine and the McGowan Institute for Regenerative Medicine. Early findings from a human trial of the process and from animal studies were published today in Science Translational Medicine. When a large volume of muscle is lost, typically due to trauma, the body cannot sufficiently respond to replace it, explained senior investigator Stephen F. Badylak, D.V.M., Ph.D., M.D., professor of surgery at Pitt and deputy director of the McGowan Institute, a joint effort of Pitt and UPMC. Instead, scar tissue can form that significantly impairs strength and function. Pig bladder ECM has been used for many years as the basis for medical products for hernia repair and treatment of skin ulcers. It is the biologic scaffold that remains left behind after cells have been removed. Previous research conducted by Dr. Badylak's team suggested that ECM also could be used to regenerate lost muscle by placing the material in the injury site where it signals the body to recruit stem and other progenitor cells to rebuild healthy tissue. "This new study is the first to show replacement of new functional muscle tissue in humans, and we're very excited by its potential," Dr. Badylak said. "These are patients who can't walk anymore, can't get out of a car, can't get up and down from a chair, can't take steps without falling. Now we might have a way of helping them get better." For the Muscle Tendon Tissue Unit Repair and Reinforcement Reconstructive Surgery Research Study, which is sponsored by the U.S. Department of Defense and is continuing to enroll new participants, five men who had at least six months earlier lost at least 25 percent of leg muscle volume and function compared to the uninjured limb underwent a customized regimen of physical therapy for 12 to 26 weeks until their function and strength plateaued for a minimum of two weeks. Then, study lead surgeon J. Peter Rubin, M.D., UPMC Professor and chair of plastic surgery, Pitt School of Medicine, surgically implanted a "quilt" of compressed ECM sheets designed to fill into their injury sites. Within 48 hours of the operation, the participants resumed physical therapy for up to 26 additional weeks. The researchers found that three of the participants, two of whom had thigh injuries and one a calf injury, were stronger by 20 percent or more six months after the surgery. One thigh-injured patient improved on the "single hop test" by 1,820 percent, and the other had a 352 percent improvement in a chair lift test and a 417 percent improvement in the single-leg squat test. Biopsies and scans all indicated that muscle growth had occurred. Two other participants with calf injuries did not have such dramatic results, but both improved on at least one functional measure and said they felt better. "This work represents an important step forward in our ability to repair tissues and improve function with materials derived from natural proteins. There will be more options to help our patients," Dr. Rubin said. The study also showed six months after an injury, mice treated with ECM showed signs of new muscle growth while untreated mice appeared to form typical scars. INFORMATION: The research team includes lead authors Dr. Rubin and Brian M. Sicari, Ph. D., and others from Pitt and the McGowan Institute for Regenerative Medicine. The project was supported by research grants from the U.S. Department of the Interior; and National Institutes of Health grants AG042199 and HL76124-6. For more information about the trial, which aims to enroll 40 participants, go to http://www.mirm.pitt.edu/badylak/clinical/muscle.asp or call 412-624-5308. The U.S. Department of Defense's Limb Salvage and Regenerative Medicine Initiative and the Muscle Tendon Tissue Unit Repair and Reinforcement Reconstructive Surgery Research Study is collaboratively managed by the Office of the Secretary of Defense. The Initiative is focused on rapidly and safely transitioning advanced medical technology in commercially viable capabilities to provide wounded warriors the safest and most advanced care possible today. About the University of Pittsburgh School of Medicine As one of the nation's leading academic centers for biomedical research, the University of Pittsburgh School of Medicine integrates advanced technology with basic science across a broad range of disciplines in a continuous quest to harness the power of new knowledge and improve the human condition. Driven mainly by the School of Medicine and its affiliates, Pitt has ranked among the top 10 recipients of funding from the National Institutes of Health since 1998. In rankings recently released by the National Science Foundation, Pitt ranked fifth among all American universities in total federal science and engineering research and development support. Likewise, the School of Medicine is equally committed to advancing the quality and strength of its medical and graduate education programs, for which it is recognized as an innovative leader, and to training highly skilled, compassionate clinicians and creative scientists well-equipped to engage in world-class research. The School of Medicine is the academic partner of UPMC, which has collaborated with the University to raise the standard of medical excellence in Pittsburgh and to position health care as a driving force behind the region's economy. For more information about the School of Medicine, see http://www.medschool.pitt.edu. http://www.upmc.com/media

Contact: Anita Srikameswaran
Phone: 412-578-9193
E-mail: SrikamAV@upmc.edu Contact: Rick Pietzak
Phone: 412-864-4151
E-mail: PietzakR@upmc.edu END


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[Press-News.org] Regenerative medicine approach improves muscle strength, function in leg injuries