An Initial Study On The Effect Of BM-MSC Transplatation On Anti-Xenogeneic Rejection

OBJECTIVES: To observe the effects of the rat bone marrow mesenchymal stem cells(BM-MSCs) on the prolixferation of mouse lymphocyte in a co-culture system. Then explore the mechanisms of tolerance in xenograft induced by establishing the rat BM–MSCS to mouse mixed chimeras model with a non- myeloabalative preparative regimen.METHODS: To establish a co-culture system and divided into fore groups: GroupⅠ: mouse lymphocyte + ConA. GroupⅡ: rat BM-MSCs + mouse lymphocyte + ConA . GroupⅢ: mouse lymphocyte + rat endotheliocyte. GroupⅣ: . rat BM-MSCs + mouse lymphocyte + rat endotheliocyte. To detect the prolixferation of mouse lymphocyte in groupⅠand groupⅡand the expression of ICAM-1 and VCAM-1 of groupⅢand groupⅣ.KM mice as recipient were conditioned with sublethal whole body irradiation(WBI), followed by cytoxan(CTX) intraperitoneal injection, then 0.3ml liquid was injected within 4 h. The recipients were divided into two groups: Group A infused sodium chloride, Group B infused bone marrow mesenchymal stem cells (BM-MSCs)of rats(2×107). To explore tolerance mechanisms by performing mixed lymphocyte reaction (MLR) 18 days after transplantation, and to detect the percentage of donor origin cells in the peripheral blood lymphocytes of recipient mice18 days and 30days after transplantation. An mixed cell culture (MCR) experiment was performed in vitro by the donator's endotheliocyte cells and the lymphocytes of recipient mice 18 days after transplantation, and the expression of ICAM-1 and VCAM-1 of donator's endotheliocyte cells was detected by ELISA.RESULTS: The OD value of the co-culture system: GroupⅠ: 1.25±0.07. GroupⅡ: 0.51±0.02. Group I is higher than groupⅡ(P <0.05). Expression of ICAM-1 and VCAM-1 of the co-culture system: GroupⅢ: 569.32±81.12ng/ml, 278.6±66.4ng/ml. GroupⅣ: 398.38±23.09ng/ml, 203.1±30 ng/ml. GroupⅢis higher than groupⅣ(P <0.05).The OD value of mixed lymphocyte reaction: Group A 0.79±0.07, Group B 0.62±0.02, Group O 0.32±0.01;Group A is higher than group B(P<0.05). The chimeric rate 18 days after transplantation is 8.6%±0.2%, 30 days after transplantation is 1.8%±0.1%, chimeric rate of the former is higher(P <0.05). The expression of ICAM-1 and VCAM-1: Group A 475.90±49.52ng/ml and 220.75±38.54ng/ml; Group B 383.81±29.26 ng/ml and 158.91±17.28 ng/ml. Group B is lower than group A (P <0.05).CONLUSIONS: The rat BM-MSCs can suppress the prolixferation of mouse lymphocyte in the co-culture system. Non-myeloablative conditioning regimens for xenogeneic BM-MSCs transplantation can successfully establish rat BM–MSCS to mouse mixed chimeras model. Mixed chimeras can suppress xenogeneic lymphocytes proliferation. Xenogeneic chimeras can suppress the activation of donator endothelial cells– decrease the expression of ICAM -1 and VCAM-1.