Transplantation of multipotent cells extracted from adult skeletal muscles into the subventricular zone of adult rats

Abstract

Stem cells isolated from adult tissues may be useful for autologous cell therapy in the nervous system. In the present study we tested the ability of multipotent stem cells isolated from adult muscle to survive and respond to migratory and differentiating cues when transplanted into the adult subventricular zone (SVZ). Prior to transplantation the cells were grown as spheres that expressed doublecortin, nestin, and betaIII-tubulin, as well as the mRNAs for the receptor EphA4 and the ligands ephrin B1, ephrin B2, but not ephrin B3. Four weeks after transplantation into the anterior part of the SVZ in adult rats, surviving cells were observed along the ventricular wall, in the SVZ, and in the posterior rostral migratory stream (RMS). None of these cells stained for betaIII-tubulin or doublecortin, which are molecules expressed by migrating neuroblasts, and none were present in the more rostral regions of the RMS or the olfactory bulb. However, most surviving transplanted cells were integrated into the wall of the lateral ventricle and expressed vimentin, a marker also expressed by ependymocytes. No tumors were observed 4 weeks posttransplantation. Our results suggest that multipotent stem cells isolated from adult muscle, which can be easily and safely isolated from patients and rapidly expanded ex vivo, may provide autologous vectors for the local delivery of secreted factors to the ventricles or nearby regions.