In vitro myogenesis activation of specific muscle-derived stem cells from patients with Duchenne muscular dystrophy

Abstract

Background: Muscle-derived stem cells (MDSCs) contribute to the repair of injured muscles. However, the myogenicity of MDSCs generated from patients with Duchenne muscular dystrophy (DMD) relative to healthy individuals remains unclear.

Methods: A human DMD model was established using the stem cells prepared from muscle derived from patients with DMD (DMD-hMDSCs). The expression of myogenic lineage-specific markers in MDSCs was examined with immunofluorescence, real-time polymerase chain reaction, and western blotting.

Results: It was demonstrated that, compared with cells from healthy subjects, DMD-hMDSCs are primed to self-differentiate in growth-inducing medium (GM) and robustly differentiate into myotubes in differentiation-inducing medium(DM). This feature was termed "myogenesis activation," and it was speculated that it contributes to the depletion of myogenic progenitors. Furthermore, MDSCs consistently express pax7, but the time-course of this expression does not correlate with the expression of the myogenic lineage-specific markers.

Conclusions: The myogenesis activation in DMD-hMDSCs demonstrated in this study may provide novel mechanistic insights into DMD pathogenesis and potential therapies.

Keywords: Duchenne muscular dystrophy; Muscle derived stem cells; Myogenesis activation; Myogenicity; Pax7.