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

Abstract

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