In Vitro and In Vivo Characterization of Neurally Modified Mesenchymal Stem Cells Induced by Epigenetic Modifiers and Neural Stem Cell Environment

Mesenchymal stem cell (MSC)-mediated tissue regeneration is a promising strategy to treat several neurodegenerative diseases and traumatic injuries of the central nervous system. Bone marrow MSCs have great potential as therapeutic agents, since they are easy to isolate and expand and are capable of producing various cell types, including neural cells. Recently we developed a highly efficient methodology to produce neural stem-like and neural precursor-like cells from mice bone marrow-derived MSCs that eventually differentiate into neuronaland glial-like cells in vitro. The aim of this study is to further elucidate neural expression profile of neurally induced mesenchymal stem cells (NI-MSCs) and their ability to retain neural differentiation potential when grafted into the intact spinal cord of rats. To this end, we further characterized in vitro and in vivo properties of NI-MSCs by immunocytochemistry, Western blot, ELISA, and immunohistochemistry. Immunocytochemical data demonstrated that NI-MSCs express several mature neural markers such as B3T, GFAP MAP-2, NF-200, and NeuN, which were confirmed through Western blot. ELISA data showed that NI-MSCs release nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). In vivo studies demonstrated that grafted NI-MSCs survived after transplantation into intact spinal cord and produced cells that expressed neural markers. All these data suggest that neurally modified MSCs, induced by recently developed methodology, could be a potential source of cells to replace damaged neurons and glia in injured spinal cord, and/or to promote cell survival and axonal growth of host tissue.