Multiple sclerosis (MS) is a chronic demyelinating disease of unknown etiology that affects the CNS. While current therapies are primarily directed against the immune system, the new challenge is to address progressive MS with remyelinating and neuroprotective strategies. Here, we develop a highly reproducible protocol to efficiently derive oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes from induced pluripotent stem cells (iPSCs). Key elements of our protocol include adherent cultures, dual SMAD inhibition, and addition of retinoids from the beginning of differentiation, which lead to increased yields of OLIG2 progenitors and high numbers of OPCs within 75 days. Furthermore, we show the generation of viral and integration-free iPSCs from primary progressive MS (PPMS) patients and their efficient differentiation to oligodendrocytes. PPMS OPCs are functional, as demonstrated by in vivo myelination in the shiverer mouse. These results provide encouraging advances toward the development of autologous cell therapies using iPSCs.
Induced pluripotent stem cells are stem cells that start like as a normal cell such as a cell in the skin,you then deliver a cocktail of growth factor that reverts the cell to a stem cell,which can replicate itself and has the potential to turn into any cell type. This includes the production of myelin forming oligodendrocytes. In this study they do this from people with progressive MS. They then transplant the myelin forming cells into shiverer mice. These mice have a mutation in the myelin basic protein gene and don’t make myelin so they start to shiver or tremor because of demyelination. In this study the young mice transplanted with the myelin forming cells actually myelinate. We knew this could happen but this study shows (a) a way to generate lots of myelin-producing cells (b) there is nothing intrinsically wrong with the genetics etc that prevents myelination from occurring in people with MS and (c) you could can do this from an MSer and indeed from any MSer. Therefore you could personalise the repair. This is very interesting although we would ideally lie to see how these cells remyelinate and also how they remyelinate something that has been demyelinated for some time.