Gao Jingtao, Li Yingmei, Lu Shihong, Wang Mei, Yang Zhou, Yan Xin, Zheng Yizhou
State Key Laboratory of Experimental Hematology, Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, P.R. China.
Exp Hematol. 2009 Aug;37(8):990-7. doi: 10.1016/j.exphem.2009.05.006. Epub 2009 May 27.
This study was designed to investigate the dynamics of transmigration and engraftment of hematopoietic stem/progenitor cells (HS/PCs) from umbilical cord blood (UCB) introduced via intra-bone marrow transplantation (IBMT), which is reserved as a novel strategy for possible clinical transplantation.
The early distribution pattern and engraftment level of human HS/PCs introduced via traditional intravenous transplantation (IVT) and IBMT routes were compared in the xenotransplanted nonobese diabetic/severe combined immunodeficient mouse model by means of flow cytometric analysis and an optical imaging system.
It was obvious that a good deal of IVT-introduced donor cells were entrapped in the liver and lung, 0.06% +/- 0.01% and 0.07% +/- 0.02%, respectively. Meanwhile three to six times fewer IBMT-introduced donor cells were entrapped in recipients' liver and lung (p<0.05 and p<0.05, respectively). Superior 8-week engraftment of human cells was observed in IBMT recipients (54.019% +/- 31.338%) than in IVT recipients (12.197% +/- 10.350%) when given transplants of 1.0 x 10(4) UCB CD34(+) cells and, furthermore, human hematopoietic cell engraftment was observed in IBMT, but not in IVT recipients when given transplants of 1.0 x 10(3) UCB CD34(+) cells.
Our results demonstrated that higher levels of human hematopoietic cell engraftment in nonobese diabetic/severe combined immunodeficient recipients achieved by IBMT might be due to the superior in vivo motility potential of IBMT-introduced HS/PCs. Clinical transplantation using transplants of UCB containing limited numbers of HS/PCs might benefit from the efficient IBMT strategy.
本研究旨在探讨通过骨髓内移植(IBMT)引入的脐带血(UCB)造血干/祖细胞(HS/PCs)的迁移和植入动力学,IBMT作为一种可能的临床移植新策略。
通过流式细胞术分析和光学成像系统,在异种移植的非肥胖糖尿病/严重联合免疫缺陷小鼠模型中比较了通过传统静脉移植(IVT)和IBMT途径引入的人HS/PCs的早期分布模式和植入水平。
很明显,大量经IVT引入的供体细胞滞留在肝脏和肺中,分别为0.06%±0.01%和0.07%±0.02%。同时,经IBMT引入的供体细胞滞留在受体肝脏和肺中的数量减少了三到六倍(分别为p<0.05和p<0.05)。当移植1.0×10⁴个UCB CD34⁺细胞时,观察到IBMT受体中人类细胞的8周植入情况优于IVT受体(54.019%±31.338%),而IVT受体为(12.197%±10.350%),此外,当移植1.0×10³个UCB CD34⁺细胞时,在IBMT受体中观察到人类造血细胞植入,但在IVT受体中未观察到。
我们的结果表明,IBMT在非肥胖糖尿病/严重联合免疫缺陷受体中实现的更高水平的人类造血细胞植入可能是由于经IBMT引入的HS/PCs在体内具有更高的运动潜力。使用含有有限数量HS/PCs的UCB移植进行临床移植可能受益于高效的IBMT策略。