Roles of combination transplantation of bone marrow mesenchymal stem cells and haploid hematopoietic stem cells in the treatment of bone marrow type radiation sickness

Abstract

Objective 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 60Co 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 symptoms 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 28th d 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. Key words: Bone marrow mesenchymal stem cells; Haploid; Hematopoietic reconstitution; Graft versus host disease