SDF-1 enhances the expansion and maintenance of highly purified human hematopoietic progenitors.
The stromal-derived factor-1 (SDF-1) chemokine and its putative receptor, CXCR4, have been implicated in hematopoiesis. Here we aim to characterize the effects of cytokine-induced CXCR4 expression and SDF-1 treatment on primitive human umbilical cord blood (CB) cells in vitro. Highly purified CD34+CD38-Lin-CXCR4- blood cells were capable of forming CD34+CXCR4+ cells during short-term liquid culture, but maintained distinct erythroid and myeloid progenitor composition, similar to the parent population prior to culture. In vitro, SDF-1 enhanced the expansion and differentiation of primitive CB cells in a manner that was dependent upon both the concentration of SDF-1 and the presence of specific cytokines. In the absence of cytokine addition, cultures seeded with CD34+CD38-Lin- cells demonstrated substantial cell death; however, the addition of SDF-1 alone preferentially increased progenitor cell frequency. Our study demonstrates that induction of CXCR4 expression does not alter the differentiative potential of human blood progenitors and suggests a role for SDF-1 as a growth factor required for human hematopoiesis.
The John P Robarts Research Institute, Stem Cell Biology and Regenerative Medicine, London, Ontario, Canada.
Michael
M
Rosu-Myles
Mickie
M
Bhatia
D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology*; D016207:Cytokines / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology; D006410:Hematopoiesis / Q000187:drug effects; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects*; D006801:Humans; D019718:Receptors, CXCR4 / Q000032:analysis / Q000502:physiology; D014471:Umbilical Veins / Q000166:cytology
C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D016207:Cytokines; D019718:Receptors, CXCR4