Exp Mol Med.  2018 Jan;50(1):e425. 10.1038/emm.2017.233.

Immunomodulatory effect of CD200-positive human placenta-derived stem cells in the early phase of stroke

Affiliations
  • 1Department of Biotechnology, College of Life Science, CHA University, Gyeonggi-do, Korea. jmoon@cha.ac.kr
  • 2General Research Institute, Bundang CHA general Hospital, Seongnam-si, Korea.
  • 3Department of OB. & GYN., Bundang CHA Medical Center, CHA University, Bundang, Korea.
  • 4Department of Laboratory Animal Medicine, College of Veterinary Medicine, Seoul National University, Seoul, Korea.
  • 5Department of Neurosurgery, Bundang CHA hospital, CHA university school of medicine, Seongnam-si, Korea.

Abstract

Human placenta amniotic membrane-derived mesenchymal stem cells (AMSCs) regulate immune responses, and this property can be exploited to treat stroke patients via cell therapy. We investigated the expression profile of AMSCs cultured under hypoxic conditions and observed interesting expression changes in various genes involved in immune regulation. CD200, an anti-inflammatory factor and positive regulator of TGF-β, was more highly expressed under hypoxic conditions than normoxic conditions. Furthermore, AMSCs exhibited inhibition of pro-inflammatory cytokine expression in co-cultures with LPS-primed BV2 microglia, and this effect was decreased in CD200-silenced AMSCs. The AMSCs transplanted into the ischemic rat model of stroke dramatically inhibited the expression of pro-inflammatory cytokines and up-regulated CD200, as compared with the levels in the sham-treated group. Moreover, decreased microglia activation in the boundary region and improvements in behavior were confirmed in AMSC-treated ischemic rats. The results suggested that the highly expressed CD200 from the AMSCs in a hypoxic environment modulates levels of inflammatory cytokines and microglial activation, thus increasing the therapeutic recovery potential after hypoxic-ischemic brain injury, and further demonstrated the immunomodulatory function of AMSCs in a stroke model.


MeSH Terms

Animals
Brain Injuries
Cell- and Tissue-Based Therapy
Coculture Techniques
Cytokines
Humans*
Mesenchymal Stromal Cells
Microglia
Models, Animal
Placenta
Rats
Stem Cells*
Stroke*
Cytokines
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