Human Adult Bone Marrow-Derived Mesenchymal Stem Cells: Factors Influencing Skeletal Muscle Differentiation

Abstract

Muscle disease leads to significant mortality and morbidity worldwide, and few effective treatment options are available. Bone marrow-derived mesenchymal stem cells (MSCs) offer a highly attractive means of cell therapy, having multiple modes of action, accessible, at low risk of malignant transformation and amenable to autologous transplantation. Engraftment of transplanted MSCs into skeletal muscle has been demonstrated but spontaneous incorporation is low. The factors influencing MSC myogenicity are not fully defined, and if better understood could markedly improve therapeutic prospects. Here, we identified growth factors and culture conditions that showed significant promise in promoting myogenic differentiation of human MSCs. Culture on collagen; using skeletal muscle media (containing dexamethasone, insulin, EGF, bovine fetuin, bovine serum albumin and gentamicin); and exposure to a combination of IGF1, FGF2 and VEGF all selectively increased myogenic marker transcript expression by human MSCs. Initiating and sustaining myogenic differentiation of MSCs in vitro may be a critical step in harnessing these cells for therapy. We also showed that human MSCs aggregate with myoblasts in vitro and appear to form multi-nucleated structures expressing a range of skeletal muscle markers. Our observations provide further evidence that MSCs are a credible candidate for cellular therapy in patients with muscle disease.