HSCT联合不同剂量内皮祖细胞输注对小鼠造血重建的影响

Effects of endothelial progenitor cell combined with allogeneic bone marrow transplantation on hematopoietic reconstitution in mice

目的探讨异基因造血干细胞移植联合不同剂量内皮祖细胞（EPC）输注对移植后造血重建的影响。方法以C57BL／6小鼠为供鼠，Balb／c小鼠为受鼠，进行HSCT，输注骨髓单个核细胞数量为5×10^6个／只。仅进行HSCT者为单纯骨髓细胞移植组；行HSCT的同时经尾静脉输注供者骨髓单个核细胞诱导培养的EPC的受鼠为EPC联合移植组，EPC的输注量分别为5×10^4、1×10^5、5×10^5和1×10^6个／只。另设正常对照组和致死量照射组。观察小鼠的存活率、造血重建情况及骨髓微环境的变化。结果各EPC联合移植组小鼠存活时间长于单纯骨髓移植组，5×10^5EPC联合移植组至观察结束时存活率为100％，高于其他各组（P〈0．05）。移植后10和15d，5×10^5 EPC联合移植组外周血白细胞数量高于其他组（P〈0．05）。移植后15d，5×10^5EPC联合移植组外周血血小板数量高于其他组（P〈0．05）。5×10^5EPC联合移植组造血组织增生程度也好于其他组。5×10^5EPC联合移植组骨髓内HSC比例为（1．06±0．03）％，高于其他各组（P〈0．05）。结论小鼠异基因骨髓移植中联合输注5×10^5EPC能够有效促进造血重建，提高小鼠存活率。

Objective To explore a proper dose of endothelial progenitor cells （EPCs） administration that can achieve optimal hematopoietic improving effectiveness in a murine allogeneic hematopoietic stem cell transplantation （allo-HSCT） model. Methods Female Balb/e mice were lethally irradiated with ^60Co source, and then were injected intravenously with 5 106 bone marrow cells from C57BL/6 mice （bone marrow transplantation group）. In co-transfer experiments,5×10^4、1×10^5、5×10^5 and 1×10^6 donor EPCs （EPCs treated groups） were injected simultaneously with bone marrow cells. The recipients were monitored for survival, peripheral white blood cells, hematopoietic stem cells （HSCs） and bone marrow histology. Results Compared with bone marrow transplantation group, all EPCs treated groups had accelerated recovery of peripheral white blood cells （P（0. 115）, platelets （P〈0. 05） and HSCs （P〈0. 05）. When infused with less than 5×10^5 EPCs, these effective hematopoietic improving phenomena showed a positive correlation with the administrated doses of EPCs. However, when infused with 1 ×10^6 EPCs, the mice showed lower survival rate （P〈0.05） and slower recovery of peripheral white blood cells （P〈0. 05）, platelets （P〈0. 05） and HSCs （P〈0. 05） than 5 × 10^5 EPCs treated grpup. Bone marrow histopathology analysis confirmed the above findings. Conclusion Co-transfer with donor EPCs can improve survival rate and hematopoietic reconstitution of recipient mice in allo-HSCT, and 5 × 10^5 EPCs should be a proper dose to achieve the best effectiveness.