Umbilical cord-derived mesenchymal stem cells promote myeloid-derived suppressor cell enrichment by secreting CXCL1 to prevent graft-versus-host disease after hematopoietic stem cell transplantation

• Published in: Cytotherapy (Oxford, England) Vol. 23; no. 11; pp. 996 - 1006
• Main Authors: Wang, Rui, Wang, Xiaoqi, Yang, Shijie, Xiao, Yunshuo, Jia, Yanhui, Zhong, Jiangfan, Gao, Qiangguo, Zhang, Xi
• Format: Journal Article
• Language: English
• Published: England Elsevier Inc 01.11.2021
• Subjects: Animals; cell therapy; chemokine; Chemokine CXCL1; Graft vs Host Disease - prevention & control; Hematopoietic Stem Cell Transplantation; Humans; immunosuppression; mesenchymal stem cell; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Myeloid-Derived Suppressor Cells; Umbilical Cord; hematopoietic stem cell transplantation; mesenchymal stem cell; immunosuppression; chemokine; cell therapy
• ISSN: 1465-3249; 1477-2566
• DOI: 10.1016/j.jcyt.2021.07.009

Human mesenchymal stem cells (MSCs) from various tissues have emerged as attractive candidates for the prevention and treatment of graft-versus-host disease (GVHD). However, the molecular machinery that defines and channels the behavior of these cells remains poorly understood. In this study, the authors compared the efficacy of four tissue-derived MSC types in controlling GVHD in a murine model and investigated their immunomodulatory effects. Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) effectively decreased the incidence and severity of GVHD, which was mediated by the enrichment of myeloid-derived suppressor cells in GVHD target tissues. RNA sequencing results showed that hUCMSCs highly expressed CXCL1. These results suggest a novel prophylactic application of hUCMSCs for controlling GVHD after allogeneic hematopoietic stem cell transplantation. Experimental design illustrating endometrial tissue obtained from the second day of menstrual cycle, endometrial-derived mesenchymal stem/stromal cell (eMSC) isolation and expansion, eMSC inflammatory stimulation and eMSC profiling and functionality assessments in vitro. [Display omitted] •HUCMSCs decrease the incidence and severity of GVHD more effectively than hDMSCs, hBMSCs and hADSCs.•HUCMSCs recruit MDSCs to GVHD target tissues through the CXCL1-CXCR2 axis.