Effect of transplanted oligodendrocyte precursor cells derived from inflammatory and non-inflammatory microenvironment on remyelination in a chronic cuprizone model.

Abstract

INTRODUCTION: Multiple sclerosis is a chronic demyelinating disease of the central nervous system. Transplantation of oligodendrocyte progenitor cells (OPCs) is a promising approach to enhance remyelination; however, the influence of the OPCs' microenvironmental origin on their therapeutic efficacy remains unclear. This study compared the remyelinating capacity of OPCs isolated from inflammatory (lipopolysaccharide) and non-inflammatory (cuprizone) microenvironments after transplanting into the corpus callosum and examined their effects on extracellular matrix chondroitin sulfate proteoglycans (CSPGs). METHODS: OPCs were isolated from two microenvironments and characterized by immunocytochemistry and RT-qPCR. After transplanting, OPC homing, remyelination, gene expression, and CSPG levels were evaluated using DiI labeling, LFB staining, RT-qPCR, and immunofluorescence, respectively. RESULTS: Severe demyelination exhibited in the cuprizone group compared with healthy controls (p&#x2009;<&#x2009;0.001) by Luxol fast blue staining. Myelin content significantly increased in both transplating OPCs groups (p&#x2009;<&#x2009;0.001), with a higher impact observed in mice received OPCs isolated from cuprizone as compared with lipopolysaccharide (p&#x2009;<&#x2009;0.001). Also, RT-qPCR analysis exhibited significantly reduced MBP expression in the cuprizone group, whereas was significantly increased after OPC transplantation, particularly in the cuprizone-derived OPC group (p&#x2009;<&#x2009;0.001), whereas a lower increased with lipopolysaccharide-derived OPCs (p&#x2009;<&#x2009;0.01). MOG expression exhibited a same pattern, with a significantly increase in the cuprizone-derived OPC group compared with both the cuprizone and lipopolysaccharide-derived OPC groups (p&#x2009;<&#x2009;0.001). Additionally, Immunofluorescence analysis exhibited increasing CSPG4 levels in the cuprizone group, but significantly reduced after OPC transplantation (p&#x2009;<&#x2009;0.001). Notably, in the cuprizone-derived OPC group higher reduction of CSPG4 levels observed compare with in the lipopolysaccharide-derived OPC group (p&#x2009;<&#x2009;0.001). CONCLUSION: OPC transplantation improves remyelination and reduces the CSPG level, but the effectiveness is more related to the previous history of the OPC isolation microenvironment and the new donor.