Enhanced in vivo motility of human umbilical cord blood hematopoietic stem/progenitor cells introduced via intra−bone marrow injection into xenotransplanted NOD/SCID mouse

Abstract

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.