Multipotent Adult Progenitor Cells (MAPCs)
Gene therapy and cell therapy are two possible approaches to achieve dysferlin replacement. I propose to use adult stem cells as cell therapy for dysferlinopathies. We have recently characterized a perivascular stem cell population from the skeletal muscle, termed muscle Multipotent Adult Progenitor Cells (MAPCs). Muscle MAPCs transplanted intramuscularly into mdx mice, a mouse model for muscular dystrophy, significantly contribute to muscle regeneration. Thus, MAPCs as a stem cell source may offer many advantages over satellite cells: can be easily isolated, can be massively expanded in vitro, can be easily transduced, can be intravenously and intra-arterially transplanted achieving broad biodistribution and most importantly can be isolated from allogeneic and autologous sources. We propose to first characterize muscle stem cells from the A/J dysferlin deficient mouse model. Then, we propose to intra-arterially transplant wt MAPCs into A/J mice. This will help us determine the biodistribution and early engraftment of MAPCs into multiple muscle tissues. Finally, in order to induce long-term immune tolerance of transplanted MAPC cells, we will co-transplant of hematopoietic stem cells and MAPCs derived from the same donor into A/J mice. If successful this transplantation protocol will be studied in bigger animal models.