Human progenitor cells rapidly mobilized by AMD3100 repopulate NOD/SCID mice with increased frequency in comparison to cells from the same donor mobilized by granulocyte colony stimulating factor.
AMD3100 inhibits the interaction between SDF-1 and CXCR4, and rapidly mobilizes hematopoietic progenitors for clinical transplantation. However, the repopulating function of human cells mobilized with AMD3100 has not been characterized in comparison to cells mobilized with granulocyte-colony stimulating factor (G-CSF) in the same donor. Therefore, healthy donors were leukapheresed 4 hours after injection with AMD3100; after 10 days of drug clearance the same donor was mobilized with G-CSF, allowing a paired comparison of repopulation by mobilized cells. Transplantation of mononuclear cells (MNC) or purified CD34(+) cells was compared at limiting dilution into NOD/SCID mice. Human AMD3100-mobilized MNC possessed enhanced repopulating frequency in comparison to G-CSF-mobilized MNC from paired donors, and purified CD34(+) progenitors were at least as efficient as the G-CSF mobilized cells. The frequencies of NOD/SCID repopulating cells (SRC) were 1 SRC in 8.7 x 10(6) AMD3100-mobilized MNC compared to 1 SRC in 29.0 x 10(6) G-CSF-mobilized MNC, and 1 SRC in 1.2 x 10(5) AMD3100-mobilized CD34(+) cells compared to 1 SRC in 1.8 x 10(5) G-CSF-mobilized CD34(+) cells. Hematopoietic differentiation of transplanted progenitors was similar after AMD3100 or G-CSF-mobilization. Thus, AMD3100 mobilized peripheral blood represents a rapidly obtained, highly repopulating source of hematopoietic progenitors for clinical transplantation.
Hess
David A
DA
Department of Internal Medicine, Division of Oncology, Hematopoietic Development and Malignancy Group, Washington University School of Medicine, 4940 Parkview Place, St. Louis, MO 63110, USA.
Bonde
Jesper
J
Craft
Timothy P
TP
Craft
Timothy C
TC
Wirthlin
Louisa
L
Hohm
Sarah
S
Lahey
Ryan
R
Todt
Laura M
LM
Dipersio
John F
JF
Devine
Steven M
SM
Nolta
Jan A
JA
D000818:Animals; D018952:Antigens, CD34 / Q000097:blood; D001596:Benzylamines; D000080027:Cyclams; D006085:Graft Survival / Q000187:drug effects*; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D016298:Hematopoietic Cell Growth Factors / Q000627:therapeutic use; D019650:Hematopoietic Stem Cell Mobilization / Q000379:methods*; D018380:Hematopoietic Stem Cell Transplantation; D006571:Heterocyclic Compounds / Q000627:therapeutic use*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D019718:Receptors, CXCR4 / Q000037:antagonists & inhibitors*
D018952:Antigens, CD34; D001596:Benzylamines; D000080027:Cyclams; D016298:Hematopoietic Cell Growth Factors; D006571:Heterocyclic Compounds; D019718:Receptors, CXCR4; D016179:Granulocyte Colony-Stimulating Factor; C088327:plerixafor