Multipotency and physiological role of skeletal muscle interstitium-derived stem cells

Abstract

Multipotent stem cells, other than satellite cells, that can give rise to primary myoblasts postnatally, are present in the interstitial spaces of skeletal muscle. These stem cells show differentiation potential into mesodermal and ectodermal cell lineages, and, thus, are called skeletal muscle interstitium-derived multipotent stem cells (Sk-MSCs). They are Pax7at initial isolation; and colony-forming units of these cells typically include non-adherent type myogenic cells, while satellite cells are known to be adherent in cell culture. In these colonies, both Pax7and Pax7 + myogenic cells are produced depending on asymmetric cell division. A large number of myotubes are also formed in each colony associated with putative Pax7 + satellite cells. Interestingly, Pax7-/non-adherent myogenic cells showed basal lamina (BL) formation during cell culture, whereas Px7 + myogenic cells did not. In in vivo analysis, interstitial myogenic cells showing BL formation were detected at early stages of myogenesis in the compensatory enlarged muscle, while myogenic cells in the parent fiber BL cylinder, probably satellite cells, did not form BL. Production of BL, associated with satellite cells, is essential for the in vivo establishment of new muscle fiber formation in the interstitium with, of course, innervation and capillary supply. Thus, the multipotency of Sk-MSCs that can give rise to peripheral nerve and vascular-related cells, such as Schwann cells, perineurial cells, endothelial cells, pericyte, and vascular smooth muscle cells, may have advantages over satellite cells. Therefore, the physiological role of Sk-MSCs, as a source for postnatal new muscle fiber formation (hyperplasia) and extension of nerve-vascular networks following growth and/or severe heavy resistance exercise, needs to be further investigated.