Functional Recovery of Damaged Skeletal Muscle Through Synchronized Vasculogenesis, Myogenesis, and Neurogenesis by Muscle-Derived Stem Cells

Abstract

Background-Recent studies have shown that skeletal muscle-derived stem cells (MDSCs) can give rise to several cell lineages after transplantation. However, the potential therapeutic uses of MDSCs, the functional significance of the transplanted tissue, and vasculogenesis, myogenesis, and reconstitution of other tissues have yet to be investigated in detail. In addition, the relationship between MDSCs and mesenchymal bone marrow cells is of interest. Methods and Results-We developed a severe-damage model of mouse tibialis anterior muscle with a large deficit of nerve fibers, muscle fibers, and blood vessels. We investigated the potential therapeutic use of freshly isolated CD34 ϩ /45 Ϫ (Sk-34) cells. Results showed that, after transplantation, implanted cells give rise to myogenic, vascular (pericytes, vascular smooth muscle cells, and endothelial cells), and neural (Schwann) cells, as well as contributing to the synchronized reconstitution of blood vessels, muscle fibers, and peripheral nerves, with significant recovery of both mass and contractile function after transplantation. Investigation of Sk-34 cell transplantation to the renal capsule (nonmuscle tissue) and fluorescence in situ hybridization analysis for the transplanted muscle detecting the Y chromosome revealed the intrinsic plasticity of the Sk-34 cell population. In addition, there were no donor-derived Sk-34 cells in the muscle of lethally irradiated bone marrow-transplanted animals, indicating that the Sk-34 cells were not derived from bone marrow. Conclusions-These

Trends in Mesenchymal Stem Cells' Applications for Skeletal Muscle Repair and Regeneration

“…Given the presence of resident stem and SCs within the skeletal muscle tissue, native tissue skeletal muscle-derived MSCs (MDSCs) would appear as the favorite source for regeneration therapies [34]. In response to muscle damage, the SCs population is activated by the released biomolecules and begins to proliferate and originates large numbers of muscle progenitor cells (MPCs), which will in turn contribute to skeletal muscle structure reconstruction.…”

“…The expansion of MDSCs is possible, but as it has long been known, it leads to dedifferentiation of early committed myogenic cells [40] and loss of potential. As little as 1 day in culture following isolation and sorting hinders its engraftment potential and contribution to regeneration events, hence turning it difficult to attain relevant cell numbers for implantation [34]. Confirming this loss of potential, the implantation of freshly isolated SCs in numbers as low as 250 cells outperforms the use of as many as 1.5 × 10 5 MPCs of first passage derived from SCs expansion [35].…”

The genetic and molecular basis of muscular dystrophy: roles of cell–matrix linkage in the pathogenesis

“…Stem cell therapy may potentially overcome these issues and be a major focus in the future for the management of a broad range of muscular dystrophies. Recent studies demonstrated that bone marrow stromal cells (Dezawa et al 2005) or muscle-derived stem cells (Tamaki et al 2005) are able to generate muscle cells and can repair muscle degeneration in vivo. Reconstitution of the healthy gene into such stem cells prepared from the patients and their retransplantation might be a new potential strategy to treat muscular dystrophies.…”

Adult stem cells derived from skeletal muscle — biology and potential

“…They are also positive for myogenic markers, including desmin and Myo-D. On the contrary, MDSCs do not express hematopoietic stem cells and other blood lineage markers, such as c-Kit, CD45, CD3, CD4, CD5, CD8, and CD14 [28,38]. Reports pertaining to the production of CD34 differ: some authors have confirmed its production, while other authors consider MDSCs as CD34 negative cells [28,39,40]. It has been experimentally shown that MDSCs cultured in medium with a low serum concentration spontaneously differentiate into myotubes [37].…”