title: Human ESC-derived MSCs outperform bone marrow MSCs in the treatment of an EAE model of multiple sclerosis.
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.
authors: 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.
authors: Xiaofang
authors: X
authors: Wang
authors: Advanced Cell Technology, 33 Locke Drive, Marlborough, MA 01752, USA.
authors: Erin A
authors: EA
authors: Kimbrel
authors: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Kumiko
authors: K
authors: Ijichi
authors: Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Debayon
authors: D
authors: Paul
authors: ImStem Biotechnology, Inc., 400 Farmington Avenue, Farmington, CT 06030, USA.
authors: Adam S
authors: AS
authors: Lazorchak
authors: Advanced Cell Technology, 33 Locke Drive, Marlborough, MA 01752, USA.
authors: Jianlin
authors: J
authors: Chu
authors: Advanced Cell Technology, 33 Locke Drive, Marlborough, MA 01752, USA.
authors: Nicholas A
authors: NA
authors: Kouris
authors: Advanced Cell Technology, 33 Locke Drive, Marlborough, MA 01752, USA.
authors: Gregory J
authors: GJ
authors: Yavanian
authors: Advanced Cell Technology, 33 Locke Drive, Marlborough, MA 01752, USA.
authors: Shi-Jiang
authors: SJ
authors: Lu
authors: Department of Cell Biology, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Joel S
authors: JS
authors: Pachter
authors: Department of Neuroscience, University of Connecticut Health Center, Farmington, CT 06030, USA.
authors: Stephen J
authors: SJ
authors: Crocker
authors: Advanced Cell Technology, 33 Locke Drive, Marlborough, MA 01752, USA.
authors: Robert
authors: R
authors: Lanza
authors: 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.
authors: Ren-He
authors: RH
authors: Xu
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology*; D002490:Central Nervous System / Q000473:pathology; D004195:Disease Models, Animal; D053595:Embryonic Stem Cells / Q000166:cytology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000628:therapy*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D051379:Mice; D009103:Multiple Sclerosis / Q000473:pathology* / Q000628:therapy*