Comparative effects of insulin-like growth factor II (IGF-II) and IGF-II mutants specific for IGF-II/CIM6-P or IGF-I receptors on in vitro hematopoiesis.
This report presents the results of studies investigating the effect of insulin-like growth factor II (IGF-II) on the proliferation and differentiation of CD34+ bone marrow cells in serum-substituted liquid cultures. Bone marrow cells were enriched for CD34+ cells and then placed in liquid cultures supplemented with either interleukin 3 (IL-3) or IL-3 and c-kit ligand with and without the addition of IGF-II. When CD34+ cells were incubated with IL-3, cellularity increased throughout four weeks of culture. Cellularity was twofold greater when cultures also contained IGF-II. IGF-II also promoted an increase in cellularity in cultures with IL-3 and c-kit ligand. In combination with IL-3 or IL-3 and c-kit ligand, IGF-II promoted an earlier differentiation of granulocytes, as well as an increase in the number of megakaryocyte lineage cells. There were approximately two-fold more colony-forming units for granulocytes and macrophages (CFU-GM) and burst-forming units for erythroid cells (BFU-E) in cultures containing both IL-3 and IGF-II than in cultures with IL-3 alone. These results demonstrate that in cytokine-supplemented media, physiological concentrations of IGF-II augmented both the proliferation and differentiation of CD34+ bone marrow cells while maintaining a greater number of progenitor cells. To identify the receptors through which IGF-II enhances in vitro hematopoiesis, IGF-II was substituted with one of the mutant forms of IGF-II that selectively interacts with either IGF-II/CIM6-P receptors or with IGF-I and insulin receptors. The results with the mutant forms of IGF-II demonstrate that IGF-II augments in vitro hematopoiesis primarily through its interaction with IGF-I and possibly insulin receptors, rather than IGF-II/CIM6-P receptors.
Schwartz
G N
GN
Transplantation Therapy Section, National Cancer Institute, Bethesda, Maryland 20892, USA.
Warren
M K
MK
Sakano
K
K
Szabo
J M
JM
Kessler
S W
SW
Pashapour
A
A
Gress
R E
RE
Perdue
J F
JF
D018952:Antigens, CD34 / Q000032:analysis; D001854:Bone Marrow Cells; D002102:Cadaver; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003470:Culture Media; D006410:Hematopoiesis / Q000187:drug effects* / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics* / Q000494:pharmacology*; D007377:Interleukin-3 / Q000494:pharmacology; D008533:Megakaryocytes / Q000166:cytology; D009154:Mutation / Q000502:physiology; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D019089:Stem Cell Factor / Q000494:pharmacology
D018952:Antigens, CD34; D003470:Culture Media; D007377:Interleukin-3; D019089:Stem Cell Factor; D007335:Insulin-Like Growth Factor II; D017526:Receptor, IGF Type 1