Umbilical Cord Blood-derived Mesenchymal Stem Cells In Graft-Versus-Host Disease,the Immunoregulation Effect And Mechanism Research

Objective Although the usage of mesenchymal stem cells (MSCs) as therapy forGVHD is constantly increasing, studies on its immune regulatory function andmechanisms have been rarely known. Our study is to investigate the curative effectand mechanism of inhibition of GVHD and regulation of GVL by umbilical cordblood-derived hMSCs (UCB-hMSCs), and its effect on T cell function, in order toprovide new tools and theoretical basis to improve the effect of HSCT and reducetransplant-related complications and mortality.Methods Twenty-four patients suffered from refractory GVHD (included acute orchronic) after allo-HSCT were treated with UCB-hMSCs, and we respectivelycollected peripheral blood of patients before MSCs infusion, and two, four and eightweeks after treatment. Then, we detected the proportion of lymphocyte subsets andmature dendritic cells (DCs) by flow cytometry and the expression levels of thecytokine IL-17, Ang-2and TNF-alpha by ELISA. Meanwhile, we recorded messagesincluded evaluating the improvement of the affected organs after MSCs treatment,comparing the adverse reactions of each patients and assessing the risk of infectionand recurrence of disease.Results①the follow-up messages showed: symptoms of GVHD improved significantly, especially skin and oral mucosa involvement. Until the last follow-up,none of the surviving patients experienced relapse of the underlying disease, and theincidence of infections and other transplant complications did not increase.②Flowcytometry analysis displayed: compared the results before and after MSCstransfusion, the percentage and the absolute numbers of CD3+, CD3+CD4+andCD3+CD8+T cells decreased significantly, whereas the levels of CD4+CD25+,CD4+CD25+FoxP3+, CD4+CD25+CD127low/-, CD8+CD25+, CD8+CD25+FoxP3+, andCD8+CD25+CD127low/-cells increased obviously and reached a peak at about fourweeks after MSCs infusion; the level of mature DCs reduced and reached aminimum at about two weeks.③ELISA tests showed: in the responsed group, bothTNFα and the interleukin-17(IL-17) levels decreased clearly and reached a minimumat4and2weeks after MSCs infusion, respectively; in contrast, there were nosignificant changes in Ang-2level in all the patients.Conclusions In conclusion, our study has indicated that UCB-derived hMSCs caneffectively inhibit GVHD after allo-HSCT through multiple mechanisms. Themultiple mechanisms inclued inhibiting CD4+and CD8+T and Th17cells, reducingthe level of mature DCs, depressing the expression of TNFα, stimulating the level ofTregs and so on. In addition, the time of MSCs infusion should be comprehensiveanalysis of multiple factors, such as the monitoring of immune indexes, clinicalimprovement, the primary disease recurrence and infection.