Neuralized mesenchymal stem cells (NMSC) exhibit phenotypical, and biological evidence of neuronal transdifferentiation and suppress EAE more effectively than unmodified MSC

Abstract

In the last decade several studies employing stem cells-based therapies have been investigated as an optional treatment for multiple sclerosis. Several preclinical and few clinical studies tested the efficacy of mesenchymal stem cells as a potent candidate for such therapies. Here we suggest the option of "neuralization" of classical mesenchymal stem cells as a cellular structure that resembles neural stem cells as well as there differentiation by a unique procedure towards terminally differentiated neural cells suggesting that this cell population may be appropriate for clinical application in the CNS. We investigated whether neuralized MSC (NMSC) could promote repair and recovery after injection into mice with EAE. Injection of NMSC and differentiated NMSC starting at the onset of the chronic phase of disease improved neurological function compared to controls as well as compared to naïve MSC. Injection of NMSC and mainly differentiated correlated with a reduction in the inflammation as well as in the axonal loss/damage and reduced area of demyelination. These observations suggest that NMSC and differentiated NMSC may suggest a more potent cell-based therapy that naïve MSC in the treatment arsenal of multiple sclerosis.

Keywords: Mesenchymal Stem Cells; Neuralized Mesenchymal Stem Cells; Neuroprotection; Neurotrophic Growth Factors; Transdifferentiation.