iPS-derived early oligodendrocyte progenitor cells from SPMS patients reveal deficient in vitro cell migration stimulation

Secondary progressive multiple sclerosis (SPMS) most challenging aspect is the lack of efficient regenerative response for remyelination, which is carried out by the endogenous population of adult oligoprogenitor cells (OPCs) after proper activation. OPCs must proliferate and migrate to the lesion and then differentiate into mature oligodendrocytes. To investigate the OPC cellular component in SPMS we developed iPSCs from SPMS affected donors and age matched controls (CT). We confirmed their efficient and similar OPC differentiation capacity, although we reported SPMS-OPCs are transcriptional distinguishable from their CT counterparts. Analysis of OPC-generated conditioned media (CM) also evidenced differences in protein secretion. We further confirmed SPMS-OPC CM presents a deficient capacity to stimulate OPC in vitro migration that can be compensated by exogenous addition of specific components. Our results provide an SPMS-OPC cellular model and encouraging venues to study potential cell communication deficiencies in the progressive form of MS for future treatment strategies. Four biological replicates from SPMS adult donors (01-04) and three biological replicates from adult healthy donors (01-03) were used for analysis, iPSC reprogramming and OPC differentiation.