摘要目的 观察人骨髓间充质干细胞(BMSC)联合单倍体相合造血干细胞(HSC)移植治疗辐射重度造血损伤小鼠的效果.方法 60只C57BL/6(H-2b)与BALB/c(H-2d)杂交第1代[CB6F1(H-2b ×d)]小鼠用60Co γ射线8.0 Gy全身照射后,按照完全随机设计分为照射对照、HSC单移植和BMSC+ HSC共移植3组,每组20只.检测移植后各组小鼠存活率、外周血象、骨髓病理、骨髓细胞集落形成以及移植物抗宿主病(GVHD)评分等指标.结果 照射对照组小鼠辐照后第10天全部死于造血衰竭,平均活存时间为(7.13±0.31)d.与单移植组相比,共移植组小鼠的移植物抗宿主病(GVHD)表现和病理改变均明显减轻,GVHD评分明显降低(t=3.677、4.330、5.303、3.578,P＜0.05);共移植组的生存率和生存时间明显高于单移植组(t=3.317、5.183,P＜0.05).单移植组小鼠移植后第28天WBC(6.51±1.38)×109/L、PLT(749.56±190.72)×109/L、RBC(8.15±0.74) ×1012/L、Hb(115±10.44) g/L,回升程度低于正常水平.共移植组小鼠移植后第28天WBC (12.50 ±2.07)×109/L、PLT(968.25 ±216.62)× 109/L、RBC(9.22±1.04)×1012/L、Hb(137.57±14.89)g/L,回升程度接近正常水平.单移植组小鼠外周血象的回升速度和恢复水平明显低于共移植组小鼠(t=6.665、3.164、3.011、2.520,P＜0.05).移植后第7天共移植组小鼠骨髓抑制程度较单移植组轻,第28天共移植组小鼠骨髓新生造血灶多于单移植组.共移植组小鼠骨髓CFU-E、BFU-E、CFU-GM、CFU-GEMM集落计数在辐照后第7和28天均明显多于单移植组(t=3.625、2.966、3.020、3.536,P＜0.05;t=4.369、4.849、5.044、4.243,P＜0.05).结论 BMSC联合单倍体造血干细胞移植能促进急性骨髓型放射病造血重建及植入,降低GVHD的发生,提高移植成功率.

abstractsObjective To investigate the effect of the transplantation of human bone marrow mesenchymal stem cells (BMSC) combined with haploidentical hematopoietic stem cells (HSC) in the treatment of radiation injury in mice.Methods After 8.0 Gy total body irradiation (TBI) of 60 Co γ-rays,60 mice [CB6F1 (H-2b × d)] hybridized from C57BL/6 (H-2b) and BALB/c (H-2d) were randomly divided into 3 groups i.e.,irradiation control group (n =20),HSC single transplantation group (n =20),and BMSC and HSC co-transplantation group (n =20).The survival rate,peripheral hemogram,pathological changes and colony formation of bone marrow cells,and the graft-versus-host disease (GVHD) were tested.Results In the irradiation control group,all the mice died of hematopoietic failure on the 10th d after irradiation.Compared with the single transplantation group,the symnptoms and pathological changes of the GVHD were significantly reduced in the co-transplantation group.The score of the GVHD in the co-transplantation group was lower than that in the single transplantation (t =3.677,4.330,5.303,3.578,P ＜ 0.05).The survival rate and survival time of the co-transplantation group were significantly higher than that of the single transplantation group (t =3.317,5.183,P ＜ 0.05).At 28th d after single transplantation,the value of WBC,PLT,RBC and Hb in the single transplantation group were (1.38 6.51) ×109/L,(749.56 ± 190.72) × 109/L,(8.15 ±0.74) × 1012/L,and (115 ± 10.44) g/L,respectively,and the recovery level was lower than the normal level.At 28th d after co-transplantation,the value of WBC,PLT,RBC and Hb in the co-transplantation group were (2.07 ± 12.50) × 109/L,(968.25 ±216.62) × 109/L,(9.22 ± 1.04) × 1012/L,and (137.57 ± 14.89) g/L,respectively,and the recovery level was close to the normal level.The pick-up speed and recovery level of peripheral hemogram of the single transplantation group were significantly lower than those of the co-transplantation group (t =6.665,3.164,3.011,2.520,P ＜0.05).At 7th d after transplantation,the degree of bone marrow suppression of the co-transplantation group was less than that of the single transplantation group.At 28thd after transplantation,the new bone marrow hematopoietic oven of the co-transplantation group was higher than that of the single transplantation group.The CFU-E,BFU-E,CFU-GM,CFU-GEMM of the co-transplantation group were significantly higher than that of the single transplantation group at 7 and 28 d after transplantation (t =3.625,2.966,3.020,3.536,P ＜ 0.05;t =4.369,4.849,5.044,4.243,P ＜ 0.05).Conclusions After the bone marrow type radiation injury,the transplantation of BMSC combined with HSC can promote hematopoietic reconstruction,reduce the incidence of GVHD and improve the success rate of transplantation.