Feline Bone Marrow-Derived Mesenchymal Stem Cells Express Several Pluripotent and Neural Markers and Easily Turn into Neural-Like Cells by Manipulation with Chromatin Modifying Agents and Neural Inducing Factors

Recent studies suggest that cellular therapies that utilize mesenchymal stem cells (MSCs), especially ones that have been neurally induced (NI), may provide a functional benefit in a wide range of neurological disorders. Recently, we developed a new method for the efficient generation of neural cells from human bone marrow (BM)-derived MSCs (hMSC). Neural induction was achieved by exposing cells simultaneously to chromatin-modifying agents and neural-inducing factors. When transplanted into injured spinal cords, these NI-hMSCs survived, differentiated, promoted tissue preservation, and significantly improved locomotor recovery of injured animals. In the current study, we sought to determine whether this methodological approach would be equally effective in generating neural-like cells from feline BM-derived MSCs (fMSC). Our long-term goal is to develop an autologous source of neural stem cells that can be used in cellular replacement therapies in large animal (feline) models of neurological disorders. Our results showed that fMSCs exhibited a neural morphology after 48-72 h of neural induction. Immunocytochemistry, ELISA, Western blot, and real-time RT-PCR studies revealed a higher level of expression of several pluripotent and neural genes in NI-fMSCs, the majority of which were expressed in untreated fMSCs at relatively low levels. We concluded that the expression of pluripotency- and neural-associated genes in unmodified fMSCs make them more pliable for reprogramming into a neural fate by manipulation with chromatin modifying agents and neural inducing factors.