Mobilization of long-term reconstituting hematopoietic stem cells in mice by recombinant human interleukin 7.
Administration of recombinant human interleukin 7 (rh)IL-7 to mice has been reported by our group to increase the exportation of myeloid progenitors (colony-forming unit [CFU]-c and CFU-granulocyte erythroid megakarocyte macrophage) from the bone marrow to peripheral organs (blood, spleen[s], and liver). We now report that IL-7 also stimulates a sixfold increase in the number of more primitive CFU-S day 8 (CFU-S8) and day 12 (CFU-S12) in the peripheral blood leukocytes (PBL) of mice treated with rhIL-7 for 7 d. Moreover, > 90% of lethally irradiated recipient mice that received PBL from rhIL-7-treated donor mice have survived for > 6 mo whereas none of the recipient mice that received an equal number of PBL from diluent-treated donors survived. Flow cytometry analysis at 3 and 6 mo after transplantation revealed complete trilineage (T, B, and myelomonocytic cell) repopulation of bone marrow, thymus, and spleen by blood-borne stem/progenitor cells obtained from rhIL-7-treated donor mice. Thus, IL-7 may prove valuable for mobilizing pluripotent stem cells with long-term repopulating activity from the bone marrow to the peripheral blood for the purpose of gene modification and/or autologous or allogeneic stem cell transplantation.
Grzegorzewski
K J
KJ
Biological Carcinogenesis and Development Program, Program Resources, Inc./DynCorp, Frederick, Maryland 21702-1201.
Komschlies
K L
KL
Jacobsen
S E
SE
Ruscetti
F W
FW
Keller
J R
JR
Wiltrout
R H
RH
D000818:Animals; D006410:Hematopoiesis / Q000187:drug effects*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006412:Hematopoietic Stem Cells / Q000166:cytology*; D015851:Interleukin-7 / Q000494:pharmacology*; D016131:Lymphocyte Subsets / Q000166:cytology; D008221:Lymphoid Tissue / Q000166:cytology; D051379:Mice; D008810:Mice, Inbred C57BL; D011828:Radiation Chimera; D011994:Recombinant Proteins; D013997:Time Factors
D015851:Interleukin-7; D011994:Recombinant Proteins