efficient generation of myelinating oligodendrocytes from primary progressive multiple sclerosis patients by induced pluripotent stem cells

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ID: 171054
2014
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Abstract
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.
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douvaras2014stemefficient Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Panagiotis Douvaras, Jing Wang, Matthew Zimmer, Stephanie Hanchuk, Melanie A. O'Bara, Saud Sadiq, Fraser J. Sim, James Goldman, Valentina Fossati
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Journal nature reviews gastroenterology & hepatology
Year 2014
DOI
10.1016/j.stemcr.2014.06.012
URL
http://www.sciencedirect.com/science/article/pii/S2213671114001982
Keywords
medicine (general)biology (general)

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