title: Clinical and pathological effects of intrathecal injection of mesenchymal stem cell-derived neural progenitors in an experimental model of multiple sclerosis.
abstract: 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. MSC-NPs 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.
authors.affiliation: Multiple Sclerosis Research Center of New York, 521W. 57th St., 4th floor, New York, NY 10019, USA.
authors.forename: Violaine K
authors.initials: VK
authors.lastname: Harris
authors.forename: Qi Jiang
authors.initials: QJ
authors.lastname: Yan
authors.forename: Tamara
authors.initials: T
authors.lastname: Vyshkina
authors.forename: Sadia
authors.initials: S
authors.lastname: Sahabi
authors.forename: Xinhe
authors.initials: X
authors.lastname: Liu
authors.forename: Saud A
authors.initials: SA
authors.lastname: Sadiq
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D005260:Female; D007278:Injections, Spinal; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020528:Multiple Sclerosis, Chronic Progressive / Q000276:immunology / Q000473:pathology / Q000601:surgery*; D058953:Neural Stem Cells / Q000502:physiology / Q000637:transplantation*