University of Louisville
Adult Oligodentrocyte Precursor Cells Differentiate Into Schwann Cells Following Transplantation Into Ethidium Bromide-Induced Demyelination in the Adult Rat Spinal Cord
Institution
University of Louisville
Faculty Advisor/ Mentor
Scott D. Whittemore
Abstract
Experimental models of spinal cord demyelination in which astrocytes are lost are primarily remyelinated by Schwann cells (SC). The source of remyelinating SCs in astrocyte-ablated spinal cord lesions has been attributed to invasion from peripheral nerve roots and peripherally innervated spinal vasculature. Recent studies, however, have demonstrated potential for postnatal CNS-derived precursors to differentiate into SCs. Moreover, we recently demonstrated adult oligodendrocyte precursor cell (OPC) recruitment in areas which eventually undergo SC remyelination after ethidium bromide (EB)-induced demyelination. To determine if adult OPCs are capable of mediating SC remyelination, purified OPCs from spinal cords of adult human-placental alkaline phosphatase (hPAP) expressing rats were obtained by immunopanning with the A2B5 antibody. FACS analysis of OPCs revealed that most cells expressed A2B5 (98%), O4 (81%), and NG2 (93%). No cells expressed the SC marker p75 indicating a lack of Schwann cell lineage contamination. OPCs were transplanted acutely (3 dpi) into EB-lesioned rat spinal cords. Immunohistochemistry for hPAP demonstrated survival and integration of transplanted OPCs within EB lesions five weeks after injury. Characteristic ringlike patterns of hPAP+ processes ensheathing NF+ axons were observed. Engrafted cells did not express markers for OPCs or astrocytes. Interestingly a significant proportion of hPAP+ processes co-labeled with the Schwann cell-specific myelin protein P0. Electron microscopic immunohistochemistry demonstrated transplanted cells ensheathing axons with a characteristic Schwann cell morphology. Present data suggest that the macroglial-free environment of acute EB lesions promotes Schwann cell-like differentiation of adult OPCs and elucidates a surprising potential for these cells.
Adult Oligodentrocyte Precursor Cells Differentiate Into Schwann Cells Following Transplantation Into Ethidium Bromide-Induced Demyelination in the Adult Rat Spinal Cord
Experimental models of spinal cord demyelination in which astrocytes are lost are primarily remyelinated by Schwann cells (SC). The source of remyelinating SCs in astrocyte-ablated spinal cord lesions has been attributed to invasion from peripheral nerve roots and peripherally innervated spinal vasculature. Recent studies, however, have demonstrated potential for postnatal CNS-derived precursors to differentiate into SCs. Moreover, we recently demonstrated adult oligodendrocyte precursor cell (OPC) recruitment in areas which eventually undergo SC remyelination after ethidium bromide (EB)-induced demyelination. To determine if adult OPCs are capable of mediating SC remyelination, purified OPCs from spinal cords of adult human-placental alkaline phosphatase (hPAP) expressing rats were obtained by immunopanning with the A2B5 antibody. FACS analysis of OPCs revealed that most cells expressed A2B5 (98%), O4 (81%), and NG2 (93%). No cells expressed the SC marker p75 indicating a lack of Schwann cell lineage contamination. OPCs were transplanted acutely (3 dpi) into EB-lesioned rat spinal cords. Immunohistochemistry for hPAP demonstrated survival and integration of transplanted OPCs within EB lesions five weeks after injury. Characteristic ringlike patterns of hPAP+ processes ensheathing NF+ axons were observed. Engrafted cells did not express markers for OPCs or astrocytes. Interestingly a significant proportion of hPAP+ processes co-labeled with the Schwann cell-specific myelin protein P0. Electron microscopic immunohistochemistry demonstrated transplanted cells ensheathing axons with a characteristic Schwann cell morphology. Present data suggest that the macroglial-free environment of acute EB lesions promotes Schwann cell-like differentiation of adult OPCs and elucidates a surprising potential for these cells.