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CD56+ Muscle Derived Cells but Not Retinal NG2+ Perivascular Cells of Nonhuman Primates are Myogenic after Intramuscular Transplantation in Immunodeficient Mice

Daniel Skuk and Jacques P Tremblay

Some reports attributed to pericytes and other perivascular cells (PCs), regardless of their origin, optimal properties for cell therapy in myology. The retina is an ideal tissue to obtain pericytes and one study reported that PCs from the mouse retina were myogenic in vitro. Given the importance of nonhuman primates (NHPs) for translational research, we compared the in vivo myogenicity of NHP retinal PCs and satellite cell derived myoblasts (SCDMs) by transplantation in immunodeficient mice. We used a protocol to culture retinal pericytes of large mammals with macaque retinas. By flow cytometry, 76%-78% of the cultured cells were NG2+. CD56+ SCDMs from another macaque were proliferated in vitro. Both Tibialis anterior muscles of 4 SCID mice were injected with 1x106 cells in saline (SCDMs in the right muscles and PCs in the left), using cardiotoxin to induce muscle regeneration. They were sampled 1 month later and analyzed by histology. In SCDM-grafted muscles, NHP nuclei were abundant, in large regions with numerous NHP-derived myofibers, and some of them were Pax7+. PC-grafted muscles showed no muscle regeneration, have few NHP nuclei in small regions devoid of myofibers, and no NHP-myofibers or Pax7+ NHP nuclei were observed. Therefore, NHP SCDMs, but not retinal NG2+ PCs, regenerated muscle in vivo in immunodeficient mice.