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Use of Mesenchymal Stem/Stromal Cells for Pediatric Orthopedic Applications

Guess, Adam J. MS*; Abzug, Joshua M. MD; Otsuru, Satoru MD, PhD

doi: 10.1097/BTO.0000000000000351

Cell-based therapies using mesenchymal stem/stromal cells (MSCs) have been extensively investigated both in preclinical and clinical settings. Because of their multipotency, MSCs have initially been expected to regenerate tissues by differentiating into native tissue cells. However, accumulating evidence suggests that the observed clinical benefits are largely from the trophic effects of MSCs. In pilot studies, systemic infusion of MSCs has been shown to clinically improve patients with osteogenesis imperfecta and hypophosphatasia even though donor cell engraftment was minimal, suggesting that the trophic effects of MSCs likely play a critical role in the treatment of these pediatric orthopedic diseases. Interestingly, genomic and proteomic analyses demonstrate variance in trophic activities among MSCs from different sources and donors, suggesting that the clinical outcomes could be dependent on the selection of therapeutic MSCs. The purpose of this review is to provide current information regarding MSCs that involve their therapeutic effects and review the clinical outcomes of MSC therapy in pediatric orthopedic diseases. In addition, the potential of cell-free therapy using extracellular vesicles released by MSCs is discussed. Understanding the mechanisms underlying MSC therapeutic actions is critical to selecting therapeutic MSCs for infusion, which will increase the efficacy and consistency of MSC therapy.

*Cell-Based Therapies, cGMP Clinical Manufacturing Facility, The Research Institute at Nationwide Children’s Hospital, Columbus, OH

Department of Orthopaedics, University of Maryland School of Medicine, Baltimore, MD

The authors declare that they have nothing to disclose.

For reprint requests, or additional information and guidance on the techniques described in the article, please contact Satoru Otsuru, MD, PhD, at or by mail at Department of Orthopaedics, University of Maryland, Baltimore School of Medicine, 20 Penn St., HSFII S111, Baltimore, MD 21209. You may inquire whether the author(s) will agree to phone conferences and/or visits regarding these techniques.

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