Human Amniotic Mesenchymal Stem Cells Alleviate aGVHD after allo-HSCT by Regulating Interactions between Gut Microbiota and Intestinal Immunity

Abstract

Acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation poses one of the most vexing challenges. Gut microbiota dysbiosis can proceed aGVHD and mesenchymal stem cells (MSCs) have promising therapeutic potential for aGVHD. However, whether hAMSCs affect the gut microbiota during aGVHD mitigation remains unknown. Accordingly, we sought to define the effects and underlying mechanisms of human amniotic membrane-derived MSCs (hAMSCs) regulating the gut microbiota and intestinal immunity in aGVHD. By establishing humanized aGVHD mouse models and hAMSCs treatment, we found that hAMSCs significantly ameliorated aGVHD symptoms, reversed the immune imbalance of T cell subsets and cytokines, and restored intestinal barrier. Moreover, the diversity and composition of gut microbiota were improved upon treatment with hAMSCs. Spearman’s correlation analysis showed that there was a correlation between the gut microbiota and tight junction proteins, immune cells as well as cytokines. Our research suggested that hAMSCs alleviated aGVHD by promoting gut microbiota normalization and regulating the interactions between the gut microbiota and intestinal barrier, immunity. Graphical Abstract

Therapeutic Effects of HLA-G5 Overexpressing hAMSCs on aGVHD After Allo-HSCT: Involving in the Gut Microbiota at the Intestinal Barrier

“… 7 , 42 Understanding the interaction between the intestinal barrier and gut microbiota is essential to maintain the intestinal homeostasis and may promote the advancement of aGVHD treatment. 42 Our recent research has found that hAMSCs may improve aGVHD by regulating the interaction between gut microbiota and intestinal immunity, 12 and therefore, we sought to explore whether overexpressing HLA-G5 in hAMSCs has the same effect on the gut microbiota. Here, we found that the hAMSCs had the capability to repair intestinal barrier damage, as manifested by the increased expressions of ZO-1 and Occludin as well as decreased plasma levels of D-LA and DAO, where these indicators represent the intestinal barrier function and intestinal permeability.…”

“… 9 Human amniotic mesenchymal stem cells (hAMSCs) are a type of novel MSCs derived from post-partum placenta, a medical waste, which could be obtained easily, massively and safely without invasive procedures and ethical or moral disputes compared with bone marrow mesenchymal stem cells (BM-MSCs), making them an ideal source of MSCs for GVHD therapy. 10 We have demonstrated that hAMSCs are yet a favorable therapeutic strategy beneficial to aGVHD, 11 and the gut microbiota could be altered after hAMSCs treatment, 12 but the mechanism remains unclear.…”