GAS6 From CD200+ Adipose-Derived Stem Cells Mitigates Colonic Inflammation in a Macrophage-Dependent Manner
| Autor: | Zhen-Xing Liang, Hua-Shan Liu, Li Xiong, Zi-Wei Zeng, Xiao-Bin Zheng, Liang Kang, Ping Lan, Xian-Rui Wu |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | Journal of Crohn's and Colitis. 17:289-301 |
| ISSN: | 1876-4479 1873-9946 |
| DOI: | 10.1093/ecco-jcc/jjac123 |
| Popis: | Background and Aims Stem cell therapy is a promising cell-based treatment modality for inflammatory bowel diseases [IBD], but its application is limited by the nature of cell heterogeneity. Methods Single-cell RNA-sequencing was performed on the adipose-derived stem cells [ADSCs]. The in vitro immunomodulatory effect of ADSCs was evaluated by co-culturing with human CD4+ T cells or macrophages. The in vivo therapeutic value of ADSCs was assessed using a murine colitis model induced by dextran sulphate sodium [DSS] or 2,4,6-trinitrobenzene sulphonic acid [TNBS]. Results CD200+ ADSCs were identified as a novel subpopulation of ADSCs, based on gene ontology analysis of immunoregulatory functions. The immunoregulatory functions of these cells were further confirmed by co-culturing with CD4+ T cells or macrophages. Administration of CD200+ ADSCs effectively reduced intestinal inflammation in IBD mice models. Furthermore, we found CD200+ ADSCs-derived GAS6 exerted protective effects on experimental colitis by promoting macrophage M2 polarization via the Mer/PI3K/Akt/GSK3β signalling pathway. Conclusions This study uncovered the heterogeneity in ADSCs, in which CD200+ ADSCs presents as an alternative to conventional treatment of IBD. |
| Databáze: | OpenAIRE |
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