The neural transdifferentiation potential of bone marrow mesenchymal stem cells.

Abstract

Multiple sclerosis is a chronic inflammatory disease of the central nervous system characterized by demyelination and neuronal degeneration. Currently, there is no treatment that can promote remyelination or axonal repair and thus improve patient outcomes. Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic approach in multiple sclerosis due to their regenerative and immunomodulatory properties. Priming MSCs toward neural- or glial-like cells may enhance their therapeutic potential. Bone marrow MSCs from multiple sclerosis patients were cultured in differentiation medium containing growth factors for induction of glial and neural transdifferentiating process. Functional assays were used to characterize the proliferation and migration rates of undifferentiated and transdifferentiating MSCs. In addition, immunostaining with five different markers was performed as well as mass spectrometry to investigate and compare protein expressions among the cell types. Proliferation and migration rates of MSCs decreased in glial and neural transdifferentiating cells. The immunostaining showed expression of neuro-glial markers, and the mass spectrometry data demonstrated substantial variance in protein expression in transdifferentiating MSCs compared to undifferentiated MSCs. Glial and neural markers were upregulated in the transdifferentiating MSCs, while MSC markers were downregulated. The results demonstrate that MSCs can be guided toward a neuro-glial lineage in vitro and that the transdifferentiating process continues over several weeks. Future research should investigate the in vitro and in vivo therapeutic differences between different transdifferentiating lengths.