Demonstration of immunomodulatory properties for the human MuStem cell population, a promising candidate for cell therapy of muscular dystrophies

Over the last eighteen years, the identification of stem cells in adult tissue opened new opportunities in cellbased therapy strategy. However, allogeneic cell transplantation protocols are highly limited by graft rejection. To overcome this issue, long-term immunosuppression (IS) are classically used, resulting in improved cell engraftment but also major adverse effects. Recently, many in vitro studies demonstrated pleiotropic immunomodulatory properties for adult stem cells, especially mesenchymal ones that have been shown to modulate the behavior of many immune cells through paracrine secretion or direct contact. These features could increase their ability to engraft in allogeneic recipient despite the lack of strong IS, thus improving their therapeutic efficiency. In addition, delivery of cells with immune privilege behavior may be beneficial in the context of degenerative disorders to limit chronic inflammation that characterizes tissues and interfere with the repair process. In the lab, we isolated muscle-derived stem cells (termed MuStem cells) from healthy dogs and demonstrated that their systemic delivery in dystrophic dogs submitted to continuous IS lead to muscle regeneration and long-term clinical status stabilization. Interestingly, an IS restricted to the transplantation period was shown to be sufficient to sustain their transplantation benefits and to prevent host immunity response in allogeneic context, suggesting a possible immune privilege behaviour for the hMuStem cells. Recently, human MuStem cells were isolated and characterized as exhibiting in vitro/in vivo myogenic potential, positioning them as a promising candidate for muscle-dedicated regenerative medicine. The aim of the present study is to explore the immunological-related features of hMuStem cells and more specifically the interaction with T-cell features and the complement system activation, two key effectors of allograft rejection