Stem cells, blood vessels, and angiogenesis as major determinants for musculoskeletal tissue repair

Abstract

This manuscript summarizes 20 years of research from my laboratories at the University of Pittsburgh and more recently, at the University of Texas Health Science Center at Houston and the Steadman Philippon Research Institute in Vail, Colorado. The discovery of muscle-derived stem cells (MDSCs) did not arise from a deliberate search to find a novel population of muscle cells with high regenerative potential, but instead was conceived in response to setbacks encountered while working in muscle cell transplantation for Duchenne muscular dystrophy (DMD). DMD is a devastating inherited X-linked muscle disease characterized by progressive muscle weakness due to lack of dystrophin expression in muscle fiber sarcolemma. Although the transplantation of normal myoblasts into dystrophin-deficient muscle can restore dystrophin, this approach has been hindered by limited survival (less than 1%) of the injected cells. The fact that 99% of the cells were not surviving implantation was seen as a major weakness with this technology by most. My research team decided to investigate which cells represent the 1% of the cells surviving post-implantation. We have subsequently confirmed that the few cells which exhibit high survival post-implantation also display stem cell characteristics, and were termed "muscle-derived stem cells" or MDSCs. Herein, I will describe the origin of these MDSCs, the mechanisms of MDSC action during tissue repair, and finally the development of therapeutic strategies to improve regeneration and repair of musculoskeletal tissues. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 9999:1-9, 2018.

Bone Marrow Concentrate Injection Treatment Improves Short-term Outcomes in Symptomatic Hip Osteoarthritis Patients: A Pilot Study

“…The importance of physical activity for individuals with degenerative joint disease and its relation to age-related diseases has been well described. 5,6,13,15,18,23 Treating hip OA symptoms with BMC as opposed to conventional treatments may be an effective treatment modality in preventing comorbidity development and promoting physical activity. Our results suggest that BMC treatment has a beneficial effect on hip outcomes and function, but further evaluation of postprocedure physical activity should be considered in future studies.…”

Innovative Therapeutic Approaches for Duchenne Muscular Dystrophy

“…In the past few years, different kinds of stem cells with myogenic potential in skeletal muscle were identified, including unipotent skeletal muscle-specific stem cells, like muscle satellite cells [110], multipotent elements such as muscle-derived stem cells (MDSCs) [111], and mesangioblasts [112].…”

Therapeutic aspects of cell signaling and communication in Duchenne muscular dystrophy

“…Experiments in mice revealed that paracrine signaling between SCs and FAPs supports myogenesis by influencing the proliferation and differentiation of SCs [167] while depletion of FAPs results in lessening of the SC pool, regenerative deficit, and muscle atrophy [73]. Some interstitial cells may also have myogenic potential, including myoendothelial [168], CD133 + [169,170], PW1 interstitial [171], muscle-derived stem cells (MDSCs) [172,173], Twist2 + progenitor [174] and muscle side population cells [167,175]. Nonetheless, it is important to note that they are unable to regenerate muscle in the absence of SCs [176].…”