Muscle reconstitution by muscle satellite cell descendants with stem cell-like properties

Abstract

Recent studies have demonstrated that a distinct subpopulation with stem cell-like characteristics in myoblast culture is responsible for new muscle fiber formation after intramuscular transplantation. The identification and isolation of stem-like cells would have significant implications for successful myogenic cell transfer therapy in human muscle disorders. Using a clonal culture system for mouse muscle satellite cells, we have identified two cell types, designated `round cells' and `thick cells', in clones derived from single muscle satellite cells that have been taken from either slow or fast muscle. Clonal analysis of satellite cells revealed that the round cells are immediate descendants of quiescent satellite cells in adult muscle. In single-myofiber culture, round cells first formed colonies and then generated progeny, thick cells, that underwent both myogenic and osteogenic terminal differentiation under the appropriate culture conditions. Thick cells, but not round cells, responded to terminal differentiation-inducing signals. Round cells express Pax7, a specific marker of satellite cells, at high levels. Myogenic cell transfer experiments showed that round cells reconstitute myofibers more efficiently than thick cells. Furthermore, round cells restored dystrophin in myofibers of mdx nude mice, even when as few as 5000 cells were transferred into the gastrocnemius muscle. These results suggest that round cells are satellite-cell descendants with stem cell-like characteristics and represent a useful source of donor cells to improve muscle regeneration.

The Skeletal Muscle Satellite Cell: The Stem Cell That Came in From the Cold

“…It is still unclear if these alternative satellite cell fates represent trans-differentiation or amplification of distinct subpopulations within the satellite cell niche. The observations of Hashimoto et al (2004) that single satellite cells can give rise to anatomically different progenitor types cells-myogenic ''round cells'' and ''thick cells'' that can give rise to myogenic and osteogenic cells-seems to support the notion of separate subpopulations within satellite cells. Moreover, in salamander, satellite cells (Pax71ve) appear to contribute multipotential cells both in culture and during limb regeneration in vivo (Morrison et al 2006).…”

Functional analysis of homeodomain-containing transcription factor Lbx1 in satellite cells of mouse skeletal muscle

“…Satellite cells were prepared by a method that was essentially the same as that described by Hashimoto et al (Hashimoto et al, 2004). Briefly, muscles of 3 or 12 week old ICR mice were digested with 2.5% collagenase type I (Sigma) in DMEM for approximately 1 hour to yield single intact fibers.…”

Osteogenic properties of human myogenic progenitor cells

“…In mice, descendants of muscle satellite cell undergo osteogenic differentiation only when exposed to BMPs in vitro (Asakura et al, 2001;Hashimoto et al, 2004;Wada et al, 2002). In the absence of BMPs, these cells preferentially undergo myogenic terminal differentiation in vitro.…”