化疗对造血微环境的影响及化疗后回输自体骨髓基质细胞对造血功能恢复的作用

Influence of chemotherapy on hematopoietic microenvironment and effect of autologous bone marrow stromal cell infusion on the recovery of hematopoiesis after chemotherapy

目的 观察化疗对造血祖细胞、造血微环境的影响 ,化疗后回输体外扩增的自体骨髓基质细胞 (ABMSC)对造血功能恢复的作用。方法 对化疗患者进行骨髓CFU GM、CFU E、BFU E及基质细胞集落 (CFU F)培养、长期骨髓培养 ,观察基质层融合情况 ,计算基质层覆盖率及完全融合时间。长期化疗的 10例患者进行自身前后对照 ,在同一化疗方案下 ,单纯化疗与化疗后回输体外扩增的ABMSC[(1.1～ 8.7)× 10 8/次 ]作对比 ,观察两者造血恢复情况。结果 ①长期化疗组的CFU GM、BFU E、CFU E、CFU F显著低于正常对照组及短期化疗组 ,后两组差异无显著性 ;②三组基质层覆盖率及完全融合时间差异无显著性 ;③长期化疗组ABMSC输注后的CFU GM、CFU E、BFU E、CFU F显著高于未输注组 ;④输注ABMSC后白细胞计数及血小板计数降至最低点的值显著高于未输注组 ,前者白细胞计数及血小板计数恢复正常时间较后者明显缩短 ;⑤基质细胞回输过程及输后临床观察无不良反应。结论 长期化疗明显损伤造血祖细胞、基质祖细胞 ,但对骨髓基质细胞融合功能无明显影响 ,化疗后给予ABMSC可加速造血功能的恢复。

Objective To observe the influence of chemotherapy on hematopoietic progenitor cells (HPC) and hematopoietic microenvironment (HME). To observe whether intravenous infusion of autologous bone marrow stromal cells (ABMSC) expanded in vitro can improve the hematopoietic function. Methods Cultures of CFU GM,BFU E,CFU E and stromal progenitor cells (CFU F) from normal control and chemotherapeutic patients were performed. The stromal function was analyzed by the assessment of the area of flask surface covered by stromal cells (ASSC) and the time when stromal cells reach confluence (TC). The recovery of hematopoietic function in short term chemotherapy group and long term chemotherapy ,with or without ABMSC infusion (1.1～8.7)×10 8 post chemotherapy groups was observed. Results The yields of CFU GM,BFU E,CFU E and CFU F in long term chemotherapy group were significantly lower than that in normal group or in short term chemotherapy group. There was no significant difference among three groups in the ASSC and TC. In long term chemotherapy group, the yields of CFU GM, CFU E, BFU E and CFU F after chemotherapy with BMSC infusion were significantly higher than that without BMSC infusion. In long term chemotherapy group, the lowest value of white blood cell (WBC) and platelet after chemotherapy with BMSC infusion was significantly higher than that without BMSC infusion. The times for WBC and platelets recovered to normal were significantly shorter in BMSC group than in without BMSC. No adverse reaction was observed with ABMSC infusion. Conclusion Long term chemotherapy results in severe impairment in HPC and mesenchymal progenitor cell (MPC), but has no obvious influence on the in vitro BMSC confluent layer formation. Intravenous infusion of expanded ABMSC can accelerate the recovery of hematopoiesis after chemotherapy.