表达SDF-1/HOXB4融合基因的间充质干细胞联合脐血CD34^+干细胞共移植对辐射损伤小鼠的影响

Effects of the co-transplantation of mesenchymal stem cells expressing SDF-1/ HOXB4 fusion gene and umbilical cord blood CD34+hematopoietic stem cells on radiation-injured mice

目的观察表达SDF-1/HOXB4融合基因的间充质干细胞(mesenchymal stem cells,MSCs)联合脐血CD34+造血干细胞(hematopoietic stem cells,HSCs)共移植对辐射损伤小鼠的影响。方法表达SDF-1、HOXB4和SDF-1/HOXB4基因的3个腺病毒载体分别转染正常人骨髓MSCs,将其联合脐血CD34+细胞经尾静脉移植到辐射损伤的NOD/SCID小鼠体内(MSCs 8×105细胞/只,CD34+1×105细胞/只),分别为SDF-1/MSCs+CD34+组(SDF-1组)、HOXB4/MSCs+CD34+组(HOXB4组)、SDF1-HOXB4/MSCs+CD34+组(S-H组),另外3组为未转染MSCs+CD34+组(MSC-HSC组)、单纯CD34+组(HSC组)、单纯辐照组(IR组)。检测移植后各组小鼠存活率、外周血象恢复、骨髓病理变化及人源CD45+细胞植入率。结果 S-H组小鼠存活率高,且外周血WBC、HGB、PLT和骨髓造血功能恢复快。在移植后6周骨髓CD45+细胞植入率(47.43%±8.89%)较其余各组高。结论表达SDF-1/HOXB4融合基因的间充质干细胞(MSCs)联合脐血CD34+造血干细胞(HSCs)共移植能促进造血重建及植入,提高移植成功率。

To observe the effects of the co-transplantation of mesenchymal stem cells （MSCs） expressing SDF-1/HOXB4 fusion gene and human umbilical cord blood CD34＋ hematopoietic stem cells （HSCs） on radiation-injured mice, human bone marrow-derived MSCs were infected by different recombinant adenovirus respective expressing exogenous SDF-1, HOXB4 or SDF-1/HOXB4 gene. Then the cells were transplanted in combination of human umbilical cord blood CD34＋ hematopoietic stem cells into NOD/SCID female mice （8 ×10^5 MSCs /mouse, 1 ×10^5 CD34＋ HSCs/mouse）. The experimental groups were named as SDF-1/MSCs＋CD34＋（SDF-1）, HOXB4/MSCs＋CD34＋ （HOXB4） and SDF1-HOXB4/MSCs＋CD34＋（S-H）, while three control groups were irradiation-only （IR）, primary MSCs ＋CD34 ＋ transplantation （MSC-HSC） and CD34 ＋ transplantation （HSC） groups. After the transplantation, indexes of survival rate, peripheral blood, bone marrow pathological changes and human CD45＋ cell engraftment rate were monitored in all groups. We found that mice in S-H group presented faster recovery and higher survival rate compared with other groups. Furthermore, S-H group also enjoyed a higher CD45 ＋ cell implantation rate （47.43%±8.89%） compared to the other groups 6 weeks later. In conclusion, co-transplantation of mesenchymal stem cells expressing SDF-1/HOXB4 fusion gene and umbihcal cord blood CD34＋ hematopoietic stem ceils is capable of enhancing hematopoietic reconstitution and elevating transplantation achievement rate.