In vitro expansion of murine hematopoietic progenitor cells by leukemia inhibitory factor, stem cell factor, and interleukin-1 beta.
Murine hematopoietic progenitor cells were markedly expanded in the presence of leukemia inhibitory factor (LIF), interleukin (IL)-1 beta and/or stem cell factor (SCF), although SCF+IL-1 beta +IL-3, LIF+SCF+IL-3, and SCF+IL-1 beta showed an appreciable effect on the in vitro expansion of hematopoietic progenitor cells as well. In the presence of LIF+SCF+IL-1 beta, highly proliferative potential colony-forming units (CFU-HPP) and colony forming units of mixed lineages (CFU-Mix) were more efficiently expanded than colony forming units granulocytes/macrophage (CFU-GM) and burst-forming units of erythroid lineage (BFU-E) compared with the colony formations of freshly obtained bone marrow cells. The cell yield on day 5 in the presence of LIF+SCF+IL-1 beta was comparable to that in SCF+IL-1 beta and SCF+IL-1 beta +IL-3. Nevertheless, colony formations were marked in LIF+SCF+IL-1 beta, thus suggesting that this combination can generate hematopoietic progenitor cells that possess greater potential for CFU-HPP, CFU-Mix, CFU-GM, and BFU-E colony formations. Hematopoietic cells expanded in the presence of LIF+SCF+IL-1 beta showed increased mRNA expressions of IL-1 beta, IL-3, IL-6, granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage (GM)-CSF, interferon gamma (IFN-gamma), and LIF compared with those of nontreated hematopoietic cells. Furthermore, LIF+SCF+IL-1 beta induced increased IL-3 and GM-CSF mRNA expression in hematopoietic cells but induced decreased macrophage inflammatory protein 1 alpha (MIP1 alpha) mRNA expression as compared with SCF+IL-1 beta +IL-3. These results suggest that the balance between stimulatory and inhibitory cytokines plays an important role in in vitro expansion of hematopoietic progenitor cells.
Imamura
M
M
Third Department of Internal Medicine, Hokkaido University School of Medicine, Sapporo, Japan.
Zhu
X
X
Han
M
M
Kobayashi
M
M
Hashino
S
S
Tanaka
J
J
Kobayashi
S
S
Kasai
M
M
Asaka
M
M
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D007375:Interleukin-1 / Q000494:pharmacology*; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008222:Lymphokines / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D019089:Stem Cell Factor / Q000494:pharmacology*
D016207:Cytokines; D006131:Growth Inhibitors; D007375:Interleukin-1; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; C507838:Lif protein, mouse; D008222:Lymphokines; D019089:Stem Cell Factor