Characterization of an Injury Induced Population of Muscle-Derived Stem Cell-Like Cells

Kinga Vojnits,Haiying Pan,Yong Li,Xiaodong Mu

doi:10.1038/srep17355

Abstract

We recently discovered a novel population of stem cells from the injured murine skeletal muscle. These injury induced muscle-derived stem cell-like cells (iMuSCs) are partially reprogrammed from differentiated myogenic cells and display a pluripotent-like state. The iMuSCs exhibit stem cell properties including the ability to differentiate into multiple lineages, such as neurogenic and myogenic differentiations; they also display a superior migration capacity that demonstrating a strong ability of muscle engraftment in vivo. IMuSCs express several pluripotent and myogenic stem cell markers; have the capability to form embryoid bodies and teratomas, and can differentiate into all three germ layers. Moreover, blastocyst microinjection showed that the iMuSCs contributed to chimeric embryos but could not complete germline transmission. Our results indicate that the iMuSCs are in a partially reprogrammed state of pluripotency, which are generated by the microenvironment of injured skeletal muscle.

Highlights

Tissue repair after injury is a complex biological process, which involves the activation of tissue-resident precursors and stem cells, and a variety of infiltrating cells responding to local and systemic signals
Three days after the cell isolation, proliferating induced muscle-derived stem cell-like cells (iMuSCs) (~0.1% of the entire muscle cell population) appeared in the culture dishes; no cells were present in the cultures that established from the control, uninjured muscles (Fig. 1b)
Microscopic evaluation revealed that representative iMuSCs were 5–7 μ m in diameter, contained relatively large nuclei and a narrow rim of cytoplasm

Summary

Introduction

Tissue repair after injury is a complex biological process, which involves the activation of tissue-resident precursors and stem cells, and a variety of infiltrating cells responding to local and systemic signals. Mammalian skeletal muscle regeneration relies on the activation and proliferation of the resident muscle precursor cells[1,2] including satellite cells and muscle stem cells (MuSCs), which are populations of mononucleated cells located between the basal lamina and sarcolemma of muscle fibers. MuSCs are a functionally heterogeneous population of cells and have variable proliferation rates, marker expression profiles, self-renewal capacities, clonogenicity and differentiation capacities[2,3]. We have shown that iMuSCs express CD34, Sca[1] (Stem cell antigen-1), and Pax[7] (Paired box protein 7), and presented strong myogenic differentiation and muscle regeneration abilities in vivo[5]. We demonstrated that iMuSCs demonstrate stem cell behaviors, and are capable of differentiating into non-myogenic lineages, such as CD31+ endothelial-like cells in the healed skeletal muscle[4]. We further investigate the unique nature of the iMuSCs, focusing on their morphology, marker expression profile, pluripotency, migratory abilities and differentiation potential

Methods

Results

Conclusion