iPS细胞来源的嵌合体胸腺移植促进异基因骨髓移植小鼠的T细胞重建和抑制移植物抗宿主病

Induced Pluripotent Stem Cells-derived chimeric Thymus transplantation enhances T cells Reconstitution and prevents GVHD in Murine after allogeneic Bone Marrow Transplantation

目的:探讨诱导性多能干细胞(i PS细胞)来源的嵌合体胸腺移植(TT)对异基因骨髓移植小鼠的T细胞重建和移植物抗宿主病(GVHD)的影响。方法:将i PS细胞来源的嵌合体胸腺,植入异基因骨髓内骨髓移植(IBM-BMT)受体小鼠的肾被膜下,4周后分析比较IBM-BMT组、IBM-BMT+TT组、IBM-BMT+淋巴细胞输注(DLI)组的T细胞亚群、GVHD临床评分和病理学检查。结果:IBM-BMT组、IBM-BMT+TT组、IBM-BMT+DLI组外周血CD8+T细胞比例分别为(5.52±0.83)%、(11.10±1.49)%、(8.49±0.82)%,组间差异有统计学意义(P<0.05)。IBM-BMT+TT组的CD4+T细胞比例为(9.60±0.69)%,高于IBM-BMT组(6.42±1.40)%和IBM-BMT+DLI组(8.07±0.65)%(P<0.05)。IBM-BMT组、IBM-BMT+TT的GVHD评分低于IBM-BMT+DLI组,病理表现更轻。结论:i PS细胞来源的嵌合体胸腺移植,能有效加快移植后T细胞重建,并抑制GVHD反应。

Objective To explore the effects of iPS cells-derived chimeric thymus transplantation on T cells reconstitution and graft versus host disease of routine after allo-BMT. Methods iPS cells-derived chimeric thymus was grafted under the renal capsules of mice after aliogeneic IBM-BMT. The mice were divided into three groups： IBM-BMT group, IBM-BMT ＋ TT group and IBM-BMT ＋ DLI group. Four weeks after BMT, T lymphocyte subsets in the peripheral blood were analyzed by flow cytometry, the degree and pathological examination of GVHD were observed, respectively. Results Percentage of CD8 ＋ T cells in IBM-BMT group, IBM-BMT ＋ TT group and IBM-BMT ＋ DLI group was （5.52 ± 0.83）%, （11.10 ± 1.49）% and （8.49 ± 0.82）% respectively, there was significant difference between pairwise comparisons （P 〈 0.05 ）, and percentage of CD4 ＋ T cells of the peripheral blood in IBM-BMT ＋ TT group （9.60 ± 0.69）% was significantly higher than IBM-BMT group （6.42 ±1.40）% and IBM- BMT ＋ DLI group （8.07 ± 0.65）% （P〈 0.05） . IBM-BMT group and IBM-BMT ＋ TT group showed less clinical and histopathological scoring of GVHD than IBM-BMT ＋ DLI group. Conclusion iPS cells-derived chimeric thymus transplantation could effectively accelerate T cells reconstitution and prevent GVHD after allo-BMT.