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.

Human Skeletal Muscle Stem Cell Antiinflammatory Activity Ameliorates Clinical Outcome in Amyotrophic Lateral Sclerosis Models

“…Treated Wr mice did exhibit significant improvements in motor function, although none of these mice approached the functional capabilities of wild-type mice. The choice of SkmSCs with MSC distinctiveness as a possible cell therapy in motor neuron disorders is closely related to previous experimental evidence on MSC treatments for central nervous system (CNS) diseases (27).…”

Enhanced Neuroprotective Effects of Combination Therapy with Bone Marrow-Derived Mesenchymal Stem Cells and <b><i>Ginkgo biloba</i></b> Extract (EGb761) in a Rat Model of Experimental Autoimmune Encephalomyelitis

“…Bai et al [22] showed that BMSCs promoted the proliferation of not only OPCs, but also neural precursor cells exiting the subventricular zone. Indeed, BMSCs or conditioned medium promoted differentiation and maturation of OPCs and influenced the differentiation fate of neural precursor cells by promoting oligodendrogenesis and inhibiting astrogliosis [1,22,51]. EGb761, a potent neuroprotective agent, can pass the BBB and protect neural cells, including oligodendrocytes and OPCs, from damage.…”

Stem Cell Therapy: A Promising Therapeutic Approach for Multiple Sclerosis

“…They can also differentiate into neurons and glial cells (6,7). The anti-inflammatory, low immunogenicity, and multipotency characteristics of BMSCs render them as a desirable cell source in regenerative medicine (6,7).…”