骨髓间充质干细胞静脉输注对猕猴细胞免疫功能的影响

目的 评价猕猴间充质干细胞( MSC)静脉异体输注后对细胞免疫功能的影响。方法分离培养MSC;不做其他处理，将异体MSC静脉输注给受者猴，通过定期监测外周血象、混合淋巴细胞反应( MLR)、T细胞亚群来判断MSC输注后受者细胞免疫功能的变化。结果成功培养了猕猴的MSC。异体MSC输注后，受者无明显毒性反应、排异表现及血象变化。可以在一定时间内（2周左右）抑制受者T细胞在MLR中的增殖活性，受者猴A2、A3及A4输注MSC的数量分别为4.0×105/kg、1.0×106/kg、2.0×106/kg，在输注后第14天时，MLR的相对反应值(RR)与输注前比较均明显降低，分别从(46.0±2.6)％、( 40.9±2.3)％、(48.3±2.0)％降至(40.4±1.73)％、(33.0±2.1)％、(39.0±1.0)％(F=1O.19,P=0.023；F=2.593，P= 0.013;F= 28.431,P=0.003)，输注后第30天时RR均恢复到输注前水平；统计结果显示，抑制程度(△RR)与输注MSC数量呈正相关(F=27.413，P=0.038)。A4是输注MSC数量最多的受者，输注后第14天开始，外周血CD3+、CD3+ CD4+、CD3+CD8+细胞的百分比与输注前相比有所降低，在输注后第30天左右恢复至输注前水平。结论单纯体内输注异体MSC，可以在一定时间内抑制受者T细胞的免疫活性；免疫抑制程度与输注MSC数量呈正相关。MSC特殊的免疫学特性使其具有深远的临床应用价值。

Effects on cellular immunity caused by intravenous infusion of allogenic rhesus mesenchymal stem cells

Objective To study the changes of cellular immunity caused by intravenous infusion of allogenic rhesus mesenchymal stem cells (MSCs). Methods MSCs were isolated and cultured. Then the immunomodulatory effects after MSCs infusion were evaluated by means of peripheral blood counts, mixed lymphocyte reaction (MLR) and analysis of lymphocytic subgroup. Results MSCs of rehsus were successfully cultivated. No acute toxicities or GVHD were observed in recipients. No obvious changes of peripheral blood counts were present. Recipients A2, A3, A4 were administered with MSC by 4.0 ×105/kg, 1.0 ×106/kg, 2.0×106/kg respectively and relative reaction (RR) of MLR decreased 14 days post MSCs infusion: from 46±2.6 ％to 40.4±1.73 ％ (F =10.19, P =0.023), from (40.9±2.3) ％ to (33±2.1) ％ (F =2.593, P =0.013), from 48.3±2.0 ％ to 39±1.0 ％ (F =28.431, P =0.003) respectively. The decrease degree (ARR) was positively related to the amount of MSCs(F =27.413, P =0.038). RR was restored within 30 days post MSCs infusion. After MSCs infusion, CD3+ CD3+CD4+ and CD3+CD8+ T-lymphocytes decreased in recipient A4, who was administered with the largest number of MSCs, and restored within 30 days. Conclusion MSCs infusion without any other treatment could temporarily inhibit immunity of T lymphocytes in MLR and the immunity inhibition was positively related to the amount of MSCs. The specific immunological characteristics of MSCs were demonstrated with extensive prospect in clinical research.