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 blood (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 beta1 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 (1.2%), were found to migrate preferentially towards SDF-1. In the input, 14%+/-2.5% of the BM CD34+ cells were in G2/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.
Voermans
C
C
Division of Medical Oncology, Netherlands Cancer Institute, Academic Medical Centre, University of Amsterdam.
Gerritsen
W R
WR
von dem Borne
A E
AE
van der Schoot
C E
CE
D001853:Bone Marrow; D002465:Cell Movement; D005312:Fetal Blood / Q000166:cytology*; D005353:Fibronectins; D019650:Hematopoietic Stem Cell Mobilization; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D006801:Humans
D005353:Fibronectins