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Stem Cell Reports. 2014 Jun 6;3(1):115-30. doi: 10.1016/j.stemcr.2014.04.020. eCollection 2014 Jul 8.

Human ESC-derived MSCs outperform bone marrow MSCs in the treatment of an EAE model of multiple sclerosis.

Author information

1
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030, USA ; ImStem Biotechnology, Inc., 400 Farmington Avenue, Farmington, CT 06030, USA.
2
Advanced Cell Technology, 33 Locke Drive, Marlborough, MA 01752, USA.
3
Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA.
4
Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
5
ImStem Biotechnology, Inc., 400 Farmington Avenue, Farmington, CT 06030, USA.
6
Department of Genetics and Developmental Biology, University of Connecticut Health Center, Farmington, CT 06030, USA ; ImStem Biotechnology, Inc., 400 Farmington Avenue, Farmington, CT 06030, USA ; Faculty of Health Sciences, University of Macau, Taipa, Macau, China.

Abstract

Current therapies for multiple sclerosis (MS) are largely palliative, not curative. Mesenchymal stem cells (MSCs) harbor regenerative and immunosuppressive functions, indicating a potential therapy for MS, yet the variability and low potency of MSCs from adult sources hinder their therapeutic potential. MSCs derived from human embryonic stem cells (hES-MSCs) may be better suited for clinical treatment of MS because of their unlimited and stable supply. Here, we show that hES-MSCs significantly reduce clinical symptoms and prevent neuronal demyelination in a mouse experimental autoimmune encephalitis (EAE) model of MS, and that the EAE disease-modifying effect of hES-MSCs is significantly greater than that of human bone-marrow-derived MSCs (BM-MSCs). Our evidence also suggests that increased IL-6 expression by BM-MSCs contributes to the reduced anti-EAE therapeutic activity of these cells. A distinct ability to extravasate and migrate into inflamed CNS tissues may also be associated with the robust therapeutic effects of hES-MSCs on EAE.

PMID:
25068126
PMCID:
PMC4110787
DOI:
10.1016/j.stemcr.2014.04.020
[Indexed for MEDLINE]
Free PMC Article

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