title: Cycling G1 CD34+/CD38+ cells potentiate the motility and engraftment of quiescent G0 CD34+/CD38-/low severe combined immunodeficiency repopulating cells.
abstract: The mechanism of human stem cell expansion ex vivo is not fully understood. Furthermore, little is known about the mechanisms of human stem cell homing/repopulation and the role that differentiating progenitor cells may play in these processes. We report that 2- to 3-day in vitro cytokine stimulation of human cord blood CD34(+)-enriched cells induces the production of short-term repopulating, cycling G1 CD34(+)/CD38(+) cells with increased matrix metalloproteinase (MMP)-9 secretion as well as increased migration capacity to the chemokine stromal cell-derived factor-1 (SDF-1) and homing to the bone marrow of irradiated nonobese diabetic severe/combined immunodeficiency (NOD/SCID) mice. These cycling G1 cells enhance SDF-1-mediated in vitro migration and in vivo homing of quiescent G0 CD34(+) cells, which is partially abrogated after inhibition of MMP-2/-9 activity. Moreover, the engraftment potential of quiescent G0 SCID repopulating cells (SRCs) is also increased by the cycling G1 CD34(+)/CD38(+) cells. This effect is significantly abrogated after incubation of cycling G1 cells with a neutralizing anti-CXCR4 antibody. Our data suggest synergistic interactions between accessory cycling G1 CD34(+)/CD38(+) committed progenitor cells and quiescent, primitive G0 CD34(+)/CD38(-/low) SRC/stem cells, the former increasing the motility and engraftment potential of the latter, partly via secretion of MMP-9.
authors.affiliation: The Weizmann Institute of Science, Department of Immunology, P.O. Box 26, Rehovot 76100, Israel.
authors.forename: Tamara
authors.initials: T
authors.lastname: Byk
authors.forename: Joy
authors.initials: J
authors.lastname: Kahn
authors.forename: Orit
authors.initials: O
authors.lastname: Kollet
authors.forename: Isabelle
authors.initials: I
authors.lastname: Petit
authors.forename: Sarit
authors.initials: S
authors.lastname: Samira
authors.forename: Shoham
authors.initials: S
authors.lastname: Shivtiel
authors.forename: Herzl
authors.initials: H
authors.lastname: Ben-Hur
authors.forename: Amnon
authors.initials: A
authors.lastname: Peled
authors.forename: Wanda
authors.initials: W
authors.lastname: Piacibello
authors.forename: Tsvee
authors.initials: T
authors.lastname: Lapidot
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000378:metabolism*; D000818:Animals; D018952:Antigens, CD34 / Q000378:metabolism*; D001854:Bone Marrow Cells / Q000502:physiology; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D002633:Chemotaxis; D003114:Colony-Forming Units Assay; D016207:Cytokines / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology; D016193:G1 Phase; D006801:Humans; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019718:Receptors, CXCR4 / Q000378:metabolism; D016192:Resting Phase, Cell Cycle; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000166:cytology* / Q000502:physiology
chemical_list: D018952:Antigens, CD34; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D016207:Cytokines; D019718:Receptors, CXCR4; D051997:ADP-ribosyl Cyclase 1; D020780:Matrix Metalloproteinase 9