Abstract
Skeletal muscle makes up 40–50% of body mass, and is thus considered to be a good adult stem cell source for autologous therapy. Although, several stem/progenitor cells have been fractionated from mouse skeletal muscle showing a high potential for therapeutic use, it is unclear whether this is the case in human. Differentiation and therapeutic potential of human skeletal muscle-derived cells (Sk-Cs) was examined. Samples (5–10 g) were obtained from the abdominal and leg muscles of 36 patients (age, 17–79 years) undergoing prostate cancer treatment or leg amputation surgery. All patients gave informed consent. Sk-Cs were isolated using conditioned collagenase solution, and were then sorted as CD34−/CD45−/CD29+ (Sk-DN/29+) and CD34+/CD45− (Sk-34) cells, in a similar manner as for the previous mouse Sk-Cs. Both cell fractions were appropriately expanded using conditioned culture medium for about 2 weeks. Differentiation potentials were then examined during cell culture and in vivo transplantation into the severely damaged muscles of athymic nude mice and rats. Interestingly, these two cell fractions could be divided into highly myogenic (Sk-DN/29+) and multipotent stem cell (Sk-34) fractions, in contrast to mouse Sk-Cs, which showed comparable capacities in both cells. At 6 weeks after the separate transplantation of both cell fractions, the former showed an active contribution to muscle fiber regeneration, but the latter showed vigorous engraftment to the interstitium associated with differentiation into Schwann cells, perineurial/endoneurial cells, and vascular endothelial cells and pericytes, which corresponded to previous observations with mouse SK-Cs. Importantly, mixed cultures of both cells resulted the reduction of tissue reconstitution capacities in vivo, whereas co-transplantation after separate expansion showed favorable results. Therefore, human Sk-Cs are potentially applicable to therapeutic autografts and show multiple differentiation potential in vivo.
Highlights
Skeletal muscle organ/tissue comprises 40–50% of body mass, and it undergoes marked changes postnatally as a result of physical over-load or disuse, known as muscle hypertrophy and atrophy, respectively
No CD34+/CD45+ cells were seen among human skeletal muscle-derived cells (Sk-Cs), and this is a difference from mouse SkCs (Figure 1B)
We demonstrated through in vitro and in vivo analysis that human SK-Cs could be divided into two typical cell populations that differentiate into: (1) a myogenic lineage, sorted as human Sk-DN/29+ cells; and (2) peripheral nerve support and vascular cell lineages sorted as human Sk-34 cells
Summary
Skeletal muscle organ/tissue comprises 40–50% of body mass, and it undergoes marked changes postnatally as a result of physical over-load or disuse, known as muscle hypertrophy and atrophy, respectively. Stem cells in skeletal muscle have been fractionated by various methods, including pre-plating culture series (Lee et al, 2000; Torrente et al, 2001; Qu-Petersen et al, 2002), repeated culture following the freeze-thaw technique (Williams et al, 1999; Young et al, 2001; Romero-Ramos et al, 2002) and fluorescence activated cell sorting (FACS) with cell surface makers (Tamaki et al, 2002) or with Hoechest dye (Gussoni et al, 1999; Jackson et al, 1999; Majka et al, 2003; Tamaki et al, 2003) Because of these variations in isolation/fractionation methods, it is difficult to directly compare the origin, localization and differentiation potentials of these stem cells. There are no standard methods for the isolation of practical stem cells from skeletal muscles
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
