title: Mesenchymal stem cells enhance the engraftment and myelinating ability of allogeneic oligodendrocyte progenitors in dysmyelinated mice.
abstract: Multiple sclerosis is an autoimmune disease characterized by demyelination and axonal loss throughout the central nervous system. No regenerative treatment exists for patients who fail to respond to conventional immunosuppressive and immunomodulating drugs. In this scenario, stem cell therapy poses as a rational approach for neurological regeneration. Transplantation of embryonic-derived oligodendrocyte progenitor cells (OPCs) has been shown to promote remyelination and ameliorate animal models of neurodegenerative diseases. However, its therapeutic application is limited due to potential transplant rejection. In multiple sclerosis, an added concern is that transplant rejection would be most pronounced at sites of previous lesions, exacerbating a hyperactive immune response which could prevent remyelination and precipitate additional demyelination. Routine systemic immunosuppression may not be sufficient to prevent transplant rejection-associated immune reactions in the cerebral microenvironment. Mesenchymal stem cells (MSCs), due to their homing properties and inherent immunosuppressive nature, are a promising tool for clinical application targeted toward immunosuppression at sites of injury. In this study, we used a co-transplantation strategy to investigate the effect of syngeneic MSCs on the survival and remyelination abilities of allogeneic OPCs in adult nonimmunosuppressed shiverer mice. At all time points examined, cotransplantation with MSCs increased OPC engraftment, migration, and maturation in myelinating oligodendrocytes, which produced widespread myelination in the host corpus callosum. In addition, MSCs reduced microglia activation and astrocytosis in the brain of transplanted animals as well as T-cell proliferation in vitro. These data suggest that combining the immunomodulatory and trophic properties of MSCs with the myelinating ability of OPCs might be a suitable strategy for promoting neurological regeneration in demyelinating diseases.
authors.affiliation: Multiple Sclerosis Research Center of New York, New York, New York 10019, USA.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cristofanilli
authors.forename: Violaine K
authors.initials: VK
authors.lastname: Harris
authors.forename: Aaron
authors.initials: A
authors.lastname: Zigelbaum
authors.forename: Andrea M
authors.initials: AM
authors.lastname: Goossens
authors.forename: Amy
authors.initials: A
authors.lastname: Lu
authors.forename: Hannah
authors.initials: H
authors.lastname: Rosenthal
authors.forename: Saud A
authors.initials: SA
authors.lastname: Sadiq
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D001921:Brain / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D002470:Cell Survival; D005434:Flow Cytometry; D005911:Gliosis / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007121:Immunocompetence; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009186:Myelin Sheath / Q000378:metabolism* / Q000473:pathology*; D009836:Oligodendroglia / Q000166:cytology*; D033581:Stem Cell Transplantation; D013601:T-Lymphocytes / Q000166:cytology; D016212:Transforming Growth Factor beta / Q000096:biosynthesis; D014184:Transplantation, Homologous
chemical_list: D016212:Transforming Growth Factor beta; D049452:Green Fluorescent Proteins