不同干细胞骨髓腔内输注对移植物抗宿主病和免疫耐受的影响

Influence of intra-bone marrow injection with hematopoietic stem cells of different origins upon the development of graft-versus host disease and immune tolerance

观察不同来源的造血干细胞经髓腔内输注能否在减轻移植物抗宿主病(GVHD)的同时诱导稳定的免疫耐受。雌性C57BL/6小鼠接受全身照射(TBI)预处理后,输注雄性BABL/c小鼠来源的骨髓细胞或经rhG-CSF动员后的外周造血干细胞,2 d后腹腔注射环磷酰胺(CTX)。观察各组GVHD发生情况,并通过皮肤移植对受者耐受状态进行检测。结果显示,髓腔内骨髓移植组(IBM-BMT)的受鼠无1例发生GVHD,而髓腔内外周造血干细胞移植组(IBM-PBSCT)的受鼠GVHD发生率较尾静脉组(IV)明显减低(P<0.05);IBM-BMT和IBM-PBSCT组受鼠对供鼠皮肤移植物的存活时间均超过120 d,较IV组明显延长(P<0.01)。实验表明髓腔内输注在降低GVHD发生率的同时,有利于稳定的免疫耐受状态的形成。

To determine whether the graft versus host disease（GVHD） could be alleviated and the immune tolerance could be achieved by intra-bone marrow injections of hematopoietic stem cells, female C57BL/6 mice pre-treated with total body irradiation（TBI） were injected with bone marrow cells derived from male BALB/c mice or the peripheral hematopoietic stem cells mobilized with the granulocyte-colony stimulating factor rhG-CSF. Two days later, cyclophosphamide was then injected intraperitoneally. The development of GVHD was observed and skin grafting was performed to investigate the status of immune tolerance. It was found that the recipients of mice in the intra-bone marrow tansplantation （IBM-BMT） group developed no GVHD. The frequency of GVHD in the recipients of mice after transplantation with peripheral bone marrow stem cells（IBM-PBSCT） was significantly reduced , compared with that of recipients received tail-vein injections of tranplants （IV group）（P〈0.05）and the survival time of skin-grafting in the recipient mice in IBM-BMT and IBM-PBSCT groups prolonged to more than 120 days, compared with that of the IV group（P〈0. 01）. It is concluded that intra-bone marrow injection with bone marrow stem cells can induce a stable status of immune tolerance so as to decrease the development of GVHD in the allogeneic mice.