Primary progressive multiple sclerosis (PPMS) is a chronic demyelinating disease of the central nervous system (CNS) currently lacking any effective treatment. Promoting endogenous brain repair offers a potential strategy to halt and possibly restore neurologic function in PPMS. To understand how the microenvironment within white matter lesions plays a role in repair we have focused on neural progenitor cells (NPCs) since these are found in lesions in PPMS and have been found to influence oligodendrocyte progenitor cell maturation (OPCs). To better understand the cellular nature of NPCs in PPMS we developed iPS cells from blood samples of PPMS patients and age matched non-disease spouse or blood relative controls. Using these iPS cell lines we determined that the NPCs from PPMS cases provided no neuroprotection against active CNS demyelination compared to NPCs from control iPS lines which were capable of completely preventing injury. Conditioned media (CM) from PPMS NPCs provides no protection to OPCs and prevents maturation of OPCs into oligodendrocytes in vitro. We also found that CM from PPMS iPS NPCs elicited patient-specific differences in the response to compounds that should foster oligodendrocyte (OL) maturation. Together, these data establish a new model for understanding the nature of myelination defects in PPMS which may lead to novel targeted approaches for preventing demyelination in these patients.
Nicaise AM, Banda E, Guzzo RM, Russomanno K, Castro-Borrero W, Willis CM, Johnson KM, Lo AC, Crocker SJ.iPS-derived neural progenitor cells from PPMS patients reveal defect in myelin injury response. Exp Neurol. 2016. pii: S0014-4886(16)30384-3.
IPS cells are inducuble pluripotent stem cells which means that you have taken a cell and by the means of a cocktail of signalling molecules you can make the cells regress back into a stem cell capable of making any other cell type. if you taken then from pwMS you can see if their genetics are influencing function compared to health. In this study they took blood cells and made iPS from them they were then make into neural stem cells that can make nerves, oligodendrocytes and astrocytes. In this study they found that the stem cells did not promote myelination infact they inhibted it and this is mediated by a growth/differentiation factor that the neural stem cells produce.
So the bad news is that if we think that we can simply make iPS into stem cells and transfer them into pwMS they they are unlikely to work. This indicates that there is probably a genetic predisposition that is creating the myelination block.