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Stem Cell Reports. 2014 Aug 12;3(2):250-9. doi: 10.1016/j.stemcr.2014.06.012. Epub 2014 Jul 24.

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

Author information

1
The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA.
2
Department of Pharmacology and Toxicology, School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, NY 14214, USA.
3
Tisch Multiple Sclerosis Research Center of New York, New York, NY 10019, USA.
4
Department of Pathology and Cell Biology, Columbia University, New York, NY 10032, USA.
5
The New York Stem Cell Foundation Research Institute, New York, NY 10032, USA. Electronic address: vfossati@nyscf.org.

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.

PMID:
25254339
PMCID:
PMC4176529
DOI:
10.1016/j.stemcr.2014.06.012
[Indexed for MEDLINE]
Free PMC Article

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