人脐带间充质干细胞对急性淋巴细胞白血病患儿异基因干细胞移植后免疫重建的影响

Effect of human umbilical cord mesenchymal stem cells on immune reconstruction of acute lymphoblastic leukemia children undergoing allogeneic hematopoietic stem cell transplantation

背景:人脐带间充质干细胞可分泌多种支持造血的细胞因子和生长因子,可改变造血微环境,具有调节及改善机体免疫功能的作用。目的:探讨人脐带间充质干细胞对儿童急性淋巴细胞白血病异基因造血干细胞移植后免疫重建的影响。方法:选取64例接受异基因造血干细胞移植治疗的急性淋巴细胞白血病患儿,分为非血缘性供者异基因造血干细胞移植组(allo-HSCT组,n=32)及非血缘性供者异基因造血干细胞移植后输注人脐带间充质干细胞组(allo-HSCT+MSCs组,n=32),观察两组治疗效果及并发症发生情况,比较两组患儿预处理前、移植后1,3,6个月时外周血免疫球蛋白及淋巴细胞亚群水平。结果与结论:①allo-HSCT+MSCs组粒细胞植入时间短于allo-HSCT组(P<0.05),慢性移植物抗宿主病、巨细胞病毒感染生率低于allo-HSCT组(P<0.05);②两组移植后造血干细胞植入率、血小板重建、累计复发率、1年存活率比较差异无显著性意义(P>0.05);③allo-HSCT+MSCs组移植后1,3,6个月血清免疫球蛋白IgA、IgG、IgM、IgE水平及外周血T淋巴细胞(CD4^+、CD3^+CD4^+、CD4^+CD8^+)、B细胞(CD19^+)水平均高于allo-HSCT组(P<0.05);④结果表明,联合人脐带间充质干细胞输注能有效降低急性淋巴细胞白血病患儿异基因造血干细胞移植慢性抗宿主病发生率,有助于粒细胞造血重建及免疫功能重建。

BACKGROUND:Human umbilical cord mesenchymal stem cells(hUC-MSCs)can secrete a variety of cytokines andgrowth factors to support hematopoiesis.They can change the hematopoietic microenvironment,and furthermore,regulate and improve the immune function of the organism.OBJECTIVE:To investigate the effect of hUC-MSCs on immune reconstitution and prognosis in children with acutelymphoblastic leukemia(ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).METHODS:Sixty-four ALL children who had undergo allo-HSCT were enrolled and randomized into non-blood donorallo-HSCT group(n=32)and non-blood donor allo-HSCT+hUC-MSCs group(n=32).The therapeutic effect andcomplication were observed in the two groups.The changes of immunoglobulins and lymphocyte subpopulations in thetwo groups were compared before and1,3and6months after transplantation.RESULTS AND CONCLUSION:Compared with the allo-HSCT group,the time of granulocyte implantation was shorter(P<0.05),and the incidence of chronic graft versus host disease and cytomegalovirus was lower in the allo-HSCT+hUC-MSCs group.There were no significant differences in hematopoietic stem cell implantation rate,platelet remodelingrate,cumulative recurrence rate and1-year survival rate between the two groups(P>0.05).The levels of serumimmunoglobulins IgA,IgG,IgM,IgE and the levels of T lymphocytes(CD4+,CD3+CD4+,CD4+CD8+)and B cells in theperipheral blood of allo-HSCT+hUC-MSCs group were significantly higher than those in the allo-HSCT group at1,3and6months after transplantation(P<0.05).In conclusion,the combined use of hUC-MSCs infusion and allo-HSCT caneffectively reduce the incidence of chronic graft-versus-host disease,and contribute to granulocyte hematopoieticreconstitution and immune function reconstruction.