Cord blood progenitor cells have greater transendothelial migratory activity and increased responses to SDF-1 and MIP-3beta compared with mobilized adult progenitor cells.
When cord blood is used as a source of haemopoietic stem cells for transplantation, fewer cells are required per kg of recipient. This greater engraftment efficiency of cord blood cells may relate to an increased ability to traverse sinusoidal endothelium, a crucial step in the homing of stem cells. We report that freshly isolated cord blood progenitors migrated more efficiently than mobilized adult cells. Cord blood progenitors responded rapidly to growth factor stimulation with an increase in migratory ability within 24 h whereas mobilized adult cells responded only after 72 h (P < 0.01). Cord blood cells also exited G0/G1 rapidly; after 24 h of growth factor exposure, 20.2 +/- 1.2% of cord blood CD34+ cells were in S + G2/M compared to 6.9 +/- 1.2% of adult CD34+ cells (P < 0.01). Proliferating CFC migrated more efficiently (13.3 +/- 3.4% for GM-CFC) than non-proliferating CFC (1.4 +/- 0.5%, P < 0.01) as determined using a 3H-thymidine suicide assay. Cord blood progenitor cells also demonstrated a greater transmigratory response to chemokine stimulation compared with adult cells; this was manifested as a differential response of freshly isolated cells to SDF-1, and of growth factor activated cells to MIP-3beta. Finally, cord blood CD34+ cells express higher levels of the chemokine receptor for SDF-1, CXCR4, when compared with mobilized adult CD34+ cells (P < 0. 05).
Yong
K
K
Department of Haematology, Royal Free and University College Medical School, London. kwee.yong@ucl.ac.uk
Fahey
A
A
Reeve
L
L
Nicholls
C
C
Thomas
N S
NS
Pizzey
A
A
Ings
S J
SJ
Watts
M J
MJ
Linch
D C
DC
D000328:Adult; D018952:Antigens, CD34 / Q000378:metabolism; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002453:Cell Cycle / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D054415:Chemokine CCL19; D054377:Chemokine CXCL12; D019742:Chemokines, CC / Q000494:pharmacology*; D019743:Chemokines, CXC / Q000494:pharmacology*; D004730:Endothelium, Vascular; D005312:Fetal Blood / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D019718:Receptors, CXCR4 / Q000378:metabolism
D018952:Antigens, CD34; C515460:CCL19 protein, human; C515255:CXCL12 protein, human; D015815:Cell Adhesion Molecules; D054415:Chemokine CCL19; D054377:Chemokine CXCL12; D019742:Chemokines, CC; D019743:Chemokines, CXC; D019718:Receptors, CXCR4