Influence of cell cycling and cell division on transendothelial migration of CD34+ cells.
The migration of haemopoietic stem and progenitor cells across endothelium lining bone marrow sinuses is a critical first step in the homing and successful engraftment of these cells. We have previously shown that freshly isolated mobilized peripheral blood CD34+ cells adhere to the endothelial surface but do not transmigrate unless activated by growth factors. The aim of this work was to examine the relationship between cell cycle progression, cell division and migration across endothelium. We now show that the enhanced migration of cytokine-activated cells is selective for cells which are in G0G1 phase of the cell cycle. Thus, the transmigrated population of CD34+ cells was enriched for cells in G0G1 phase, and sorted cells in G0G1 migrated more efficiently than those in S+G2M. Conversely, cells in S+G2M were more adherent to endothelium, a finding that may explain their reduced migration. Using the cytoplasmic dye, carboxyfluorescein diacetate succinimidyl ester, to track the divisional kinetics of CD34+ cells, we found that migration occurred preferentially in non-divided cells. Thus, although CD34+ cells require cytokine activation in order to migrate, cell division is not required for transmigration, which occurs optimally before cells enter S phase. The superior migratory ability of CD34+ cells in G0G1 phase of the cell cycle may have important implications for the homing and engraftment of ex vivo expanded cells.
Yong
Kwee L
KL
Department of Haematology, University College London, UK. kwee.yong@ucl.ac.uk
Fahey
Anne
A
Pizzey
Arnold
A
Linch
David C
DC
D000328:Adult; D018952:Antigens, CD34; D015415:Biomarkers / Q000032:analysis; D001842:Bone and Bones / Q000502:physiology*; D002448:Cell Adhesion; D002465:Cell Movement / Q000502:physiology; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000494:pharmacology; D004727:Endothelium; D004730:Endothelium, Vascular; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D039041:Integrin alpha4beta1 / Q000032:analysis; D007399:Interphase; D019041:L-Selectin / Q000032:analysis; D008213:Lymphocyte Activation; D008223:Lymphoma; D009101:Multiple Myeloma; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis; D019718:Receptors, CXCR4 / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology*; D014407:Tumor Cells, Cultured
D018952:Antigens, CD34; D015415:Biomarkers; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; D039041:Integrin alpha4beta1; D019384:Nucleic Acid Synthesis Inhibitors; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D019718:Receptors, CXCR4; D019041:L-Selectin; D006918:Hydroxyurea