Proliferation and clonal characterization of human muscle derived CD133+ positive stem cells define an intrinsic heterogeneity

In the muscle there exist different stem cell populations that are able to participate in muscle regeneration. How muscle stem cells balance their self-renewal capacity and their ability to differentiate are central questions in stem cell research. Moreover, recent findings supported the notion that heterogeneity is a hallmark of stem cells. It is known that these cell populations express a variety of surface markers including CD29, CD56, CD44, CD90, CD105, STRO–1. Here we have focused our attention on the so-called MDSCs (Muscle-Derived Stem Cells) that can be rather considered as satellite precursors. In the past our group focused its attention on a stem cell population expressing CD133 antigens on its surface. The analysis of muscle-derived CD133+ cells showed that they have been characterized for their regenerative potential in vivo, as well as their ability to repopulate the satellite cell niche. However, we found in the CD133+ MDSCs a phenotypic heterogeneity in the presence of some surface antigens: in the same cell population we found an oscillation of expression of endothelial, myogenic and mesenchymal markers. Based on these assumptions we sorted some cell subpopulations obtained from muscles of healthy orthopedic patients: mesenchimal-like cells (133+ 73+ 44+ 29+ 34- 45-); endothelial-like cells (133+ 90+ 146+ 31+ 45) and myogenic-like cells (133+ 56+ 45- 34+/-). These subpopulation of sorted CD133 where cloned and analyzed for their capacity to proliferate and differentiate into the endothelial and myogenic lineages. In these experiments we found stem cell properties in the mesenchymal-like CD133+ clones. In fact these cells posses clonogenic potential and well differentiate into endothelial and myogenic cells. In conclusion, our study showed that muscle-derived CD133+ cells represent an heterogeneous population of mesenchymal, myogenic and endothelial progenitors. Further experiments are needed in order to understand whether CD133 purification could be useful for clinical applications in muscular distrophies.