GAS6 From CD200+ Adipose-Derived Stem Cells Mitigates Colonic Inflammation in a Macrophage-Dependent Manner
Zhen-Xing Liang1,2,3, Hua-Shan Liu1,2, Li Xiong1,2
1Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.
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.
