T.I.4 Potential of muscle stem cells and cell therapy for Duchenne muscular dystrophy

Muscle satellite cells play central roles in postnatal muscle growth and regeneration, and therefore, are the most promising tool for cell therapy for Duchenne muscular dystrophy (DMD). Indeed, cultured satellite cells/myoblasts have been used for transplantation into DMD patients in early 90’s, but attempts continue in combination with adequate immunosupressants. Freshly isolated satellite cells participate in muscle repair more effectively than cultured satellite cells, at least in mice models, but application into human patients has not started yet. In addition to satellite cells, skeletal muscle contains other types of stem cells. Among them, muscle side population (SP) cells are heterogeneous in origin, gene expression and differentiation potential. CD31-negative CD45-negative SP cells have mesenchymal stem cell-like properties and expand during muscle regeneration. Murine or canine mesoangioblasts or human pericytes are also found to be closely associated with vessels in skeletal muscle, and have been recognized as a good source of transplantation. Italian group is now preparing clinical trials of human pericytes. AC133 positive cell is another candidate of muscle stem cells. Recently, a novel technology to induced pluripotent stem (iPS) cells from somatic cells was developed. According to the protocol described by Dr. Yamanaka’s group in Kyoto University, we generated iPS cells from dystrophin-deficient mdx mice of different age. The clones showed quite similar properties to those of ES cells. Understanding of the properties of muscle stem cells would help us to generate appropriate myogenic cells from iPS cells for cell therapy of DMD.