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Immune modulatory mesenchymal stem cells derived from human embryonic stem cells through a trophoblast-like stage
Wang X.1; Lazorchak A.S.1; Song L.1; Li E.2; Zhang Z.2; Jiang B.2; Xu R.-H.1,2
2016-02-01
Source PublicationStem Cells
ISSN15494918
Volume34Issue:2Pages:380-391
Abstract

Mesenchymal stem/stromal cells (MSCs) have great clinical potential in modulating inflammation and promoting tissue repair. Human embryonic stem cells (hESCs) have recently emerged as a potentially superior cell source for MSCs. However, the generation methods reported so far vary greatly in quality and efficiency. Here, we describe a novel method to rapidly and efficiently produce MSCs from hESCs via a trophoblast-like intermediate stage in approximately 11-16 days. We term these cells "T-MSCs" and show that T-MSCs express a phenotype and differentiation potential minimally required to define MSCs. T-MSCs exhibit potent immunomodulatory activity in vitro as they can remarkably inhibit proliferation of cocultured T and B lymphocytes. Unlike bone marrow MSCs, T-MSCs do not have increased expression of inflammatory mediators in response to IFNγ. Moreover, T-MSCs constitutively express a high level of the immune inhibitory ligand PD-L1 and elicit strong and durable efficacy in two distinct animal models of autoimmune disease, dextran sulfate sodium induced colitis, and experimental autoimmune encephalomyelitis, at doses near those approved for clinical trials. Together, we present a simple and fast derivation method to generate MSCs from hESCs, which possess potent immunomodulatory properties in vitro and in vivo and may serve as a novel and ideal candidate for MSC-based therapies.

KeywordAutoimmune Disease Cellular Therapy Differentiation Embryonic Stem Cells Immunosuppression Mesenchymal Stem Cells
DOI10.1002/stem.2242
URLView the original
Indexed BySCI
Language英语
WOS Research AreaCell Biology ; Biotechnology & Applied Microbiology ; Oncology ; Hematology
WOS SubjectCell & Tissue Engineering ; Biotechnology & Applied Microbiology ; Oncology ; Cell Biology ; Hematology
WOS IDWOS:000370353200012
PublisherWILEY-BLACKWELL, 111 RIVER ST, HOBOKEN 07030-5774, NJ USA
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Cited Times [WOS]:16   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionFaculty of Health Sciences
Corresponding AuthorWang X.; Xu R.-H.
Affiliation1.ImStem Biotechnology Inc., Farmington, Conneticut, USA
2.Faculty of Health Sciences, University of Macau, Taipa, Macau, People's Republic of China
Corresponding Author AffilicationFaculty of Health Sciences
Recommended Citation
GB/T 7714
Wang X.,Lazorchak A.S.,Song L.,et al. Immune modulatory mesenchymal stem cells derived from human embryonic stem cells through a trophoblast-like stage[J]. Stem Cells,2016,34(2):380-391.
APA Wang X..,Lazorchak A.S..,Song L..,Li E..,Zhang Z..,...&Xu R.-H..(2016).Immune modulatory mesenchymal stem cells derived from human embryonic stem cells through a trophoblast-like stage.Stem Cells,34(2),380-391.
MLA Wang X.,et al."Immune modulatory mesenchymal stem cells derived from human embryonic stem cells through a trophoblast-like stage".Stem Cells 34.2(2016):380-391.
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