人脐血源基质细胞对小鼠MHC半相合骨髓移植后GVHD的影响

目的探讨人脐血源基质细胞（hUCBDSC）对MHC半相合移植小鼠（移植物抗宿主反应）GVHD的影响及其可能机制。方法参照本室的方法从人脐血中分离培养hUCBDSC。建立小鼠MHC半相合骨髓移植GVHD模型,同时输注一定数量的hUCBDSC,观察小鼠的临床表现并进行GVHD评分,绘制Kaplan-Meier生存曲线,移植后14 d对小鼠皮肤、肝脏和小肠进行病理分析,流式细胞术分析小鼠脾脏中CD4＋Tregs的比例。结果和对照组相比,实验组的GVHD临床表现明显减轻。Kaplan-Meier生存曲线显示实验组的生存率明显高于对照组。移植后14d的病理切片HE染色结果显示实验组的病理程度显著低于对照组,脾脏CD4＋Tregs阳性率为10.5±0.7%,显著高于对照组6.6±0.5%。结论 hUCBDSC可能通过CD4＋Tregs减轻MHC半相合移植小鼠GVHD临床表现和病理变化,提高小鼠生存率。

Effect of hUCBDSC on GVHD in mice after haploidentical hematopoietic cell transplantation

Objective To explore the effect of hUCBDSC on GVHD in mice after haploidentical hematopoietic cell transplantation and its mechanism.Methods hUCBDSC were isolated and cultured from umbilical cord blood of healthy human donors according to protocols in our laboratory.Sublethally irradiated mice were subjected to haploidentical hematopoietic cell transplantation and splenic cell infusion.Meantime,the effect of cotransplanted hUCBDSC on clinical GVHD symptom in mice was observed.Kaplan-Meier survival curve was made.Pathological analysis was carried out on GVHD target tissues such as skin,liver and small intestine on day14 post transplantation.The percentage of CD4＋ Tregs in spleen was determined by flow cytometry.Results In experimental group,clinical GVHD symptoms were ameliorated and mortality was reduced compared to control group.Moreover,histopathological changes in experimental group were superior to control group.The percentage of splenic CD4＋ Tregs in experimental group was significantly higher than in control group on day14 post transplantation.Conclusion hUCBDSC may exert preventive effect on GVHD incidence and severity in mice suffering from haploidentical hematopoietic cell transplantation by mechanisms of CD4＋Tregs