Directly induced neural stem cells (iNSCs) for the treatment of progressive multiple sclerosis (PMS_iNSC). (360G-Wellcome-105795_Z_14_Z)

There is an urgent need to develop therapies that will cope with persistent inflammation and foster remyelination in the progressive phase of multiple sclerosis (MS). Stem cells possess a pleiotropic therapeutic potential that may be key in counteracting the variety of maladaptive processes that lead to disease progression/disability in MS patients. Before clinical application, we need to identify the most promising sources of stem cells for transplantation and further define their putative me chanisms of action in MS. Throughout the course of this fellowship I aim at characterizing tissue-specific, autologous, stably-expandable Neural Stem Cells (NSCs), and in so doing will assess their therapeutic properties in relevant mouse models of MS. Induced NSCs (iNSCs), obtained from mouse fibroblasts, will be transplanted in MOG-induced EAE (a model of chronic MS) and lysolecithin-treated mice (a model of focal demyelination). The in vivo assessments of immunomodulatory vs remyelinating p otential of iNSCs will be coupled by extensive ex vivo and in vitro co-culture studies. This preclinical data will allow our group to gain insight on the potential of iNSCs in modulating disease progression and further will facilitate the development of a solid preclinical platform designed to bring iNSC therapy into clinical practice.