Clinical and Pathological Effects of Intrathecal Injection of Mesenchymal Stem Cell-Derived Neural Progenitors in an Experimental Model of Multiple Sclerosis

Multiple sclerosis (MS) is associated with irreversible disability in a significant proportion of patients. At present,
there is no treatment to halt or reverse the progression of established disability. In an effort to develop
cell therapy-based strategies for progressive MS, we investigated the pre-clinical efficacy of bone marrow
mesenchymal stem cell-derived neural progenitors (MSC-NPs) as an autologous source of stem cells. MSCNPs
consist of a subpopulation of bone marrow MSCs with neural progenitor and immunoregulatory properties,
and a reduced capacity for mesodermal differentiation, suggesting that this cell population may be
appropriate for clinical application in the CNS. We investigated whether MSC-NPs could promote repair
and recovery after intrathecal injection into mice with EAE. Multiple injections of MSC-NPs starting at the
onset of the chronic phase of disease improved neurological function compared to controls, whereas a single
injection had no effect on disease scores. Intrathecal injection of MSC-NPs correlated with reduced immune
cell infiltration, reduced area of demyelination, and increased number of endogenous nestin-positive progenitor
cells in EAE mice. These observations suggest that MSC-NPs may influence the rate of repair through
effects on endogenous progenitors in the spinal cord. This study supports the use of autologous MSC-NPs
in MS patients as a means of promoting CNS repair.