Increased migration of cord blood-derived CD34+ cells, as compared to bone marrow and mobilized peripheral blood CD34+ cells across uncoated or fibronectin-coated filters

Hematopoietic progenitor cells (CD34(+) cells) migrate to the bone marrow after reinfusion into peripheral veins. Stromal cell-derived factor-1 (SDF-1) is a chemokine produced by bone marrow stromal cells that induces migration of CD34(+) cells. In this study we compared spontaneous and SDF-1-induced migration of CD34(+) cells from bone marrow (BM), peripheral blood (PB), and cord broad (CB) across Transwell filters. Under all circumstances, CB CD34(+) cells showed significantly more migration than did BM or PB CD34(+) cells. SDF-1 induced migration of BM CD34(+) cells was higher than that of PB CD34(+) cells, possibly due to differences in sensitivity; towards SDF-1. Indeed, PB CD34(+) cells showed a significantly lower expression of the receptor for SDF-1 (CXCR-4) than did BM and CB CD34(+) cells. The sensitivity to SDF-1, as measured by migration towards different concentrations of SDF-1, was identical for BM and CB-derived CD34(+) cells and correlated with their equal CXCR-4 receptor expression. Coating of the filters with the extracellular matrix protein fibronectin (FN) strongly enhanced the SDF-1-induced migration of PB CD34(+) cells (2.5 times) and of BM CD34(+) cells (1.5 times). SDF-1 induced migration of PB CD34(+) cells over FN-coated filters was blocked by antibodies against beta(1) integrins. Subsequently, analysis was performed to determine whether SDF-1 preferentially promoted migration of subsets of CD34(+) cells. Actively cycling CD34(+) cells, which were present in BM (14%) but hardly in PB (2.2%) or CB (7.2%), were found to migrate preferentially towards SDF-1. In the input, 14% +/- 2.5% of the BM CD34(+) cells were in G(2)/M and S phase, whereas in the migrated fraction 20% +/- 5.7% of the cells were actively cycling (p < 0.05). We did not observe preferential migration of phenotypically recognizable primitive CD34(+) subsets, despite the fact that CB CD34(+) cells are thought to contain a higher percentage of immature subsets. In conclusion, the relatively lower migration of PB CD34(+) cells seems to be due to a lower sensitivity towards SDF-1, and the higher migrational capacity of CB CD34(+) cells, in comparison to BM and PB CD34(+) cells, seems to have an as yet unknown intrinsic cause, The increased migration of CB CD34(+) cells may favor homing of these cells to the bone marrow, which might reduce the number of cells required for hematological reconstitution after transplantation. (C) 1999 International Society for Experimental Hematology. Published by EIsevier Science Inc.