Hematopoietic reconstitution by co-transplantation of human BM-MSCs and UCB CD34+ cells at various times in NOD/SCID mice / 中国实验血液学杂志

ABSTRACT

To investigate the effect of co-transplantation of bone marrow derived MSCs and UCB CD34+ cells at different time points on hematopoietic reconstitution, all NOD/SCID mice were sublethally exposed to irradiation of 60Co gamma ray and transplanted with UCB CD34+ with or without MSCs (3 mice per group). Animals were divided into HSC group and MSC+HSC group (M+H group). In HSC group, 1x10(6) UCB CD34+ cells for each mouse were infused within 4-6 hours after irradiation; the M+H group again was divided into 3 subgroups according to infusion sequence of MSCs and HSCs. (A) M+H simultaneously infused group MSCs and UCB CD34+ cells were infused simultaneously; (B) M+48H group MSCs were infused within 4-6 hours after irradiation, while UCB CD34+ cells were infused at 48 hours after irradiation; (C) H+48M group UCB CD34+ cells were infused within 4-6 hours after irradiation, while MSCs were infused at 48 hours after irradiation. In 3 subgroups infused amounts of MSCs and UCB CD34+ cells all were 1x10(6) cells. From the 3rd day after transplantation, 20 microl peripheral blood was collected from the retro-orbital plexus of mice every week until 42th day after transplantation. 42 days after transplantation, mice were sacrificed, and the percentages of human CD45, CD34, CD19 and CD11b in bone marrow, peripheral blood and spleen were detected by FACS. The results showed that (1) Co-transplantation of MSCs and UCB CD34+ cells simultaneously (M+H group) can mitigate the decrease of WBC and platelet levels (p<0.01) in peripheral blood, and accelated the hematopoietic recovery. While co-transplanting MSCs and UCB CD34+ cells at different time points (M+48H or H+48M), the similar effect was not observed (p>0.05). As far as platelets was concerned, the recovery of platelets in M+48H group was lagged behind that in M+H group (p<0.01). (2) Co-transplantation of MSCs at different time points enhanced the engraftment of hematopoietic cells (p<0.05 or p<0.01), compared with transplantation of CD34+ cells alone. The effect of engraftment enhancement was not lineage restriction (p>0.05). It is concluded that the ideal transplantation effect is achieved when MSCs and UCB CD34+ cells were co-transplanted at the same time, these study results provide experimental basis for clinical application of MSCs.