iPS-derived neural progenitor cells from PPMS patients reveal defect in myelin injury response.

iPS-derived neural progenitor cells from PPMS patients reveal defect in myelin injury response. Exp Neurol. 2016 Nov 16;: Authors: Nicaise AM, Banda E, Guzzo RM, Russomanno K, Castro-Borrero W, Willis CM, Johnson KM, Lo AC, Crocker SJ Abstract 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 oligo...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research