Oligodendrocytes Engineered with Migratory Proteins as Effective Graft Source for Cell Transplantation in Multiple Sclerosis

Abstract

Multiple sclerosis (MS) is characterized by widespread immunomodulatory demyelination of the central nervous system (CNS), resulting in nerve cell dysfunction. Accordingly, treatment strategies have been centered on immunodulation and remyelination, with the former primarily focused on reducing the pathology rather than enhancing myelin repair, which the latter targets. While conceding to the emerging view of heterogeneity in the pathology of MS, which precludes variations in degree of immune response (i.e., inflammation) and demyelination, the concept of enhancing myelin repair is appealing since it is likely to provide both disease-reducing and disease-inhibiting therapeutic approaches to MS. In this regard, we and several others have proposed that cell replacement therapy is an effective strategy to repair the myelin in MS. Here we hypothesize that transplantation of mouse bone marrow-derived oligodendrocytes (BMDOs) and BMDOs transfected with ephrin proteins (BMDO + ephrin), which are known to enhance cell and axonal migratory capacity, may produce therapeutic benefits in animal models of MS.