Gene expression profile of human iPS cell-derived mesoangioblasts (HIDEMs)

Mesoangioblasts are stem/progenitor cells derived from a subset of pericytes expressing alkaline phosphatase. They have been shown to ameliorate muscular dystrophies (currently incurable diseases) in different animal models and are now undergoing clinical experimentation for Duchenne muscular dystrophy. We show here that patients affected by limb-girdle muscular dystrophy 2D (LGMD2D, characterized by -sarcoglycan deficit) have a reduction of this subset of pericytes and hence mesoangioblast could not be derived for cell therapy. Therefore, we reprogrammed LGMD2D fibroblasts and myoblasts to induced pluripotent stem cells (iPSCs) and developed a protocol for the derivation of mesoangioblast-like cells from them. These cells can be expanded and genetically corrected with a muscle-specific lentiviral vector expressing human -sarcoglycan. Upon transplantation into ad hoc generated -sarcoglycan-null immunodeficient mice, they generate myofibers expressing -sarcoglycan. This approach may be useful for muscular dystrophies that show a reduction of resident progenitors and provides evidence of pre-clinical safety and efficacy of disease-specific iPSCs.

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Tedesco FS, Gerli MF, Perani L, Benedetti S, Ungaro F, Cassano M, Antonini S, Tagliafico E, Artusi V, Longa E, Tonlorenzi R, Ragazzi M, Calderazzi G, Hoshiya H, Cappellari O, Mora M, Schoser B, Schneiderat P, Oshimura M, Bottinelli R, Sampaolesi M, Torrente Y, Broccoli V, Cossu G