Johnny Huard is a Professor in the Department of Orthopaedic Surgery at McGovern Medical School at The University of Texas Health Science Center at Houston (UTHealth). Dr. Huard joins UT from the University of Pittsburgh, where he was an endowed professor and Vice Chair for the Department of Orthopaedic Surgery and Musculoskeletal Cellular Therapeutics. He also served as the Director of the Stem Cell Research Center for University of Pittsburgh School of Medicine. Huard completed his Ph.D. in Neurobiology at Laval University in Quebec before earning two post-doctoral degrees in Gene Therapy, the first from McGill University in Quebec, and the second from the University of Pittsburgh in Pittsburgh, Pennsylvania. Huard possesses extensive knowledge in the areas of gene therapy, tissue engineering & regenerative medicine applications based on the use of muscle-derived stem cells (MDSCs). His primary areas of interest are in basic stem cell biology and their translation to clinic to aid in the healing and regeneration of a variety of tissues. His team has received national and international recognition, and the technologies that they have developed have been licensed to industry. Together, Dr. Huard and his team have published over 300 peer reviewed papers, 82 book chapters, and have had 757 abstracts accepted for presentation at national and international conferences. Huard’s research has received over 80 honors and awards either locally or at national and international meetings. His research was featured on the cover of Stem Cells, Journal of Orthopaedic Research, and Molecular Therapy including several from the American Orthopaedic Society for Sports Medicine, the Orthopaedic Research Society, and the American Association of Orthopaedic Surgeons. He is active member of several professional and scientific societies including the American College of Sports Medicine, International Cartilage Repair Society, American Society for Biochemistry and Molecular Biology, and the American Association for the Advancement of Science.
Title of Abstract
Aging is characterized by the progressive erosion of tissue homeostasis and functional reserve in all organ systems. Although controversy remains as to the molecular mechanism(s) underlying the process of aging, accumulated cellular damage, including DNA damage, appears to be a major determinant of lifespan as well as age-related pathologies. Moreover, there is evidence that the accumulation of damage in stem cells renders them defective for self-renewing and regenerating damaged tissues. We have demonstrated that a population of muscle progenitor cells(MPCs) isolated from the ERCC1-deficient mouse model of accelerated aging, are defective in their proliferation abilities, differentiation capacity and resistance to oxidative stress. We have observed that intraperitoneal (IP) injections of wild-type (WT)-MPCs into Ercc1 knockout (Ercc1-/-) mice resulted in an improvement in age related pathologies. Although the mechanisms by which the transplantation of WT-MPCs extend the lifespan of these progeria mice is still under investigation, we have obtained evidence that the beneficial effect imparted by the injected cells occur through a paracrine effect that involve angiogenesis. In an attempt to determine whether the defect observed in ERCC deficient MPCs was not exclusive to this progeria model, we have isolated and characterized MPCs from another progeroid mouse models, the zinc metalloproteinase (Zmpste24) knock-out mouse, an animal model of the Hutchinson-Gilford progeria syndrome (HGPS). Similar to ERCC deficient MPCs, we have observed that Zmpste24-/- MPCs have proliferation and differentiation defects, characteristics also observed in MPCs isolated from naturally aged mice. These results suggest that the defect in MPCs is not specific to a particular model of progeria and can also be observed in naturally aged animals. Finally, we have investigated whether a defect in MPCs can also be observed in skeletal muscle disease such as Duchenne muscular dystrophy (DMD), which is a degenerative muscle disorder characterized by the lack of dystrophin expression at the sarcolemma of muscle fibers. Interestingly, DMD patients lack dystrophin from the time of birth; however, the onset of muscle weakness only becomes apparent at 4-7 years of age, which happens to coincide with the exhaustion of the MPC pool. There are several lines of evidence that support this concept including the gradual impairment of the myogenic potential of MPCs isolated from DMD patients during aging, which results in a reduction of muscle regeneration in older DMD patients. In addition to muscle weakness, DMD patients acquire osteopenia, fragility fractures, and scoliosis indicating that DMD may represent a model of premature musculoskeletal aging with a potential dysfunction in MPCs. Here, we report that dystrophin–utrophin double knockout (dko) mice, an animal model of DMD, exhibit a spectrum of degenerative changes in various musculoskeletal tissues including skeletal muscle, bone, articular cartilage, and intervertebral discs. In contrast to that observed with MPCs isolated from the mdx mice (dystrophin deficient and mild phenotype), we have recently shown a defect in the MPCs isolated from dKO mouse. We have observed that the MPC defect from the dKO mouse model appears to be age dependent and not specific to MPC since other stem cell population also appears to be affected. These results taken together support the concept that stem cell exhaustion plays a role in aging and disease.
Johnny Huard, Ph.D.
All Author Affiliations
The University of Texas Health Science Center at Houston (UTHealth)