Plasma elevation of stromal cell-derived factor-1 induces mobilization of mature and immature hematopoietic progenitor and stem cells.
The chemokine, stromal cell-derived factor-1 (SDF1), is produced in the bone marrow and has been shown to modulate the homing of stem cells to this site by mediating chemokinesis and chemotaxis. Therefore, it was hypothesized that elevation of SDF1 level in the peripheral circulation would result in mobilization of primitive hematopoietic stem and progenitor cells. SDF1 plasma level was increased by intravenous injection of an adenoviral vector expressing SDF1alpha (AdSDF1) into severe combined immunodeficient mice. This resulted in a 10-fold increase in leukocyte count, a 3-fold increase in platelets, and mobilization of progenitors, including colony-forming units-granulocyte-macrophage to the peripheral circulation. In addition, AdSDF1 induced mobilization of cells with stem cell potential, including colony-forming units in spleen and long-term reconstituting cells. These data demonstrate that overexpression of SDF1 in the peripheral circulation results in the mobilization of hematopoietic cells with repopulating capacity, progenitor cells, and precursor cells. These studies lay the foundation for using SDF1 to induce mobilization of hematopoietic stem and progenitor cells in in vivo studies. (Blood. 2001;97:3354-3360)
Hattori
K
K
James Ewing Laboratory of Developmental Hematopoiesis, Sloan-Kettering Institute for Cancer Research, 1275 York Ave., New York, NY 10021, USA.
Heissig
B
B
Tashiro
K
K
Honjo
T
T
Tateno
M
M
Shieh
J H
JH
Hackett
N R
NR
Quitoriano
M S
MS
Crystal
R G
RG
Rafii
S
S
Moore
M A
MA
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects; D002452:Cell Count; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000097:blood* / Q000235:genetics; D015870:Gene Expression; D006098:Granulocytes; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D007958:Leukocyte Count; D008264:Macrophages; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D016513:Mice, SCID; D010976:Platelet Count; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D017154:Stromal Cells / Q000378:metabolism; D014162:Transfection
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse