Plasticity and Physiological Role of Stem Cells Derived from Skeletal Muscle Interstitium: Contribution to Muscle Fiber Hyperplasia and Therapeutic Use

Abstract

Stem cells other than satellite cells that can give rise to primary myoblasts, which are able to form additional new fibers postnatally, are present in the interstitial spaces of skeletal muscle. These cells are sorted into CD34(+)/45(-) (Sk-34) and CD34(-)/45(-) (Sk-DN) cell fractions, and they are wholly (>99%) negative for Pax7 at initial isolation. 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 addition, both Pax7(-) and Pax7(+) cells are produced, depending on asymmetric cell division. A large number of myotubes are also formed in each colony, thus suggesting that putative Pax7(+) satellite cells also present in each colony. Interestingly, interstitial myogenic cells show basal lamina formation at early stages of myogenesis in response to various types of stimulation in compensatory enlarged muscle, a property that satellite cells do not possess in the parent fiber basal lamina cylinder. Basal lamina formation and production of satellite cells are essential before muscle fiber establishment in vivo. It is therefore likely that myogenic cells in skeletal muscle can be divided into two populations: 1) basal lamina-producing myogenic cells; and 2) basal lamina-non-producing myogenic cells. The latter population may be Pax7(+) satellite cells showing adherent capacity in cell culture, while the lamina-producing myogenic population derived from interstitial multipotent stem cells, which is predominant among Sk-34 and Sk-DN cells, plays a role in primary myoblast generation and shows non-adherent behavior in culture. Therefore, the physiological role of interstitial myogenic cells is as a source for new postnatal muscle fiber formation, and multinucleated muscle fibers (cells) are potentially formed clonally.

Human amniotic fluid stem cell injection therapy for urethral sphincter regeneration in an animal model

“…These results indicate the grafted hAFSCs might have undergone in situ myogenic differentiation and induced host muscle regeneration. These findings are similar to other reports of human stem cell transplantation into animals [17-19]. The details underlying the specific mechanism of action need to be investigated.…”

Origin and hierarchy of basal lamina-forming and -non-forming myogenic cells in mouse skeletal muscle in relation to adhesive capacity and Pax7 expression in vitro

“…7g, h and 10a, b. That is, non-Ad/laminin + cells were associated with small/compact laminin − /Pax7 + cells, even in cytospin preparations, indicating a strong relationship (cellular adhesions) between these aggregated cells, as if they were derived from the same clone following asymmetric cell division, as reported previously (Tamaki et al 2008(Tamaki et al , 2010a. Therefore, non-Ad/laminin + myogenic cells appear to be situated hierarchically upstream of the Ad/laminin − myogenic cells and work as primary myoblasts in vivo.…”

“…In fact, both Sk-34 and Sk-DN cells showed clonal production of both Pax7 + and Pax7 − myogenic cells in vitro based on asymmetric cell division and complete muscle fiber formation with satellite cells after cell transplantations into the non-muscle circumstances (beneath the kidney capsule) (Tamaki et al 2008). Therefore, we hypothesize that the clonal formation of muscle fibers may be possible in vivo through interstitial single Sk-34 and Sk-DN stem cells (Tamaki et al 2010a).…”

Preferential and Comprehensive Reconstitution of Severely Damaged Sciatic Nerve Using Murine Skeletal Muscle-Derived Multipotent Stem Cells

“…These cells were able to differentiate into mesodermal cells (skeletal muscle cells, vascular smooth muscle cells, pericytes and endothelial cells) and ectodermal cells (Schwann cells and perineurial cells) in vivo, and typically exerted synchronized reconstitution of the muscular, vascular and peripheral nervous system in severely damaged skeletal muscle [13]–[15]. This multipotency was confirmed by clonal cell culture and transplantation [11], [12], [15], and the hierarchy of these cells is such that Sk-DN cells are situated upstream of Sk-34 cells in the same lineage [16],[17]. These capacities of skeletal muscle-derived multipotent stem cells (Sk-MSCs) wholly match the demands in peripheral nerve regeneration, except for skeletal myogenesis.…”