Mesenchymal Stem Cells On Liver Failure Occur Via Immunomodulation

Mesenchymal stem cells (MSCs) have the potiential capacity of self-renewal and multilineage differentiation.At the present, bone marrow derived MSCs represents the major source of MSCs for cell therapy. Howerer,the bone marrow mesenchymal stem cells (bone marrow derived MSCs, BM-MSCs) have the limitation for its invasive procedure.Moreover, the frequency and multi-lineage differentiation potiential of BM-MSCs will decrease greatly with the age of patients.Therefore, more and more people paid more attention to the umbilical cord derived mesenchymal stem cells(UC-MSCs).In the study, a good method of the chronic liver failure’s therapy will be found through the study of the MSCs on biological characteristics and immunomodulation fuction and the early clinical test.In the first part, a method to isolate MSCs from the bone marrom of mouse and umbilical cord was described,then their biological charateristics and immunomodulation fuction have been studied .The results showed that MSCs had been isolated from the BM and UC successfully.and UC-MSCs showed the similar morphology and surface markers with BM-MSCs. BM-MSCs expressed CD44,Sca-1 but not expressed CD45,CD34, CD11c,CD11b,H-2,I-A;UC-MSCs expressed the CD73、CD59、HLA-A,B,C、CD44, but not expressed CD31、CD34、CD45、CD80、CD83、CD86、HLA-DR..They all had the potential differentiation into bone and adipose tissue.In the second part, the immunological characteristics of both MSCs in vitro were described.The result showed that both MSCs can suppress the proliferation of the splenoctytes of mouse or PBMC from human respectively in vitro.Under certain conditions, BM-MSCs cultured with the L-NMMA and 1400W respectively in vitro and the immunosuppression of BM-MSCs has been reversed greatly. AT the same time ,UC-MSCs were cultured with 1-MT and indomethacin respectively in vitro,the immunosuppression of UC-MSCs has been decreased .In this study, it also showed that the BM-MSCs can upregulate the expression of ICAM-1 and VCAM-1, and when Anti-ICAM-1 and Anti-VCAM-1 presented, the immunosuppression of BM-MSCs has been blocked. It indicated that ICAM-1�'�VCAM-1 were critical for the immunosuppression of BM-MSCs of the mouse.In the third part ,the animal of model of chronic liver failure was established.The effect of MSCs on chronic liver failure were to be studied through the animal mode.The result showed that the established animal mode with CCl4 was a good method.When the BM-MSCs was injected through tail vein of the mouse for a week,it had been found that BM-MSCs can improve its fuction of the liver and its serum levels decreased significantly after the the treatment of BM-MSCs.Moreever,histopathology revealed improvement .It could be concluded that MSCs may be used in early clinic study in the therapy of chronic liver failure.In the last part, clinical studies on the chronic liver failure patients with the UC-MSCs through the peripheral vein were performed. Six patients meet the standard of UC-MSCs transplantation. two month later ,the result showed that the serum levels of TBIL、PT、ALT、AST、TNF-α、INFγhad decreased obviously after treatment compared with those pre- treatment (P<0.01)and their clinical symptoms were improved obviously .No obvious adverse reaction had been found.Conculusion: the treatment of chronic liver failure patients with UC-MSCs through peripheral vein were safe and effective.