Enhanced growth of megakaryocyte colonies in culture in the presence of heparin and fibroblast growth factor.
Fibroblast growth factors (FGFs) are a family of mitogenic proteins that promote the division of most mesoderm- and neuroectoderm-derived cells. Interaction with heparin-like molecules appears to be critical for FGFs to exert their activity. We previously reported that FGF-1, FGF-2, and heparin are each capable of stimulating megakaryocytopoiesis in vitro and that heparin has a thrombopoietic effect when administered to patients with chronic immune thrombocytopenic purpura. The present study was designed to determine whether the combination of heparin and FGF results in a synergistic effect on murine megakaryocytopoiesis. In vitro, in both plasma clot and agar serum-free culture systems, FGF-1 and FGF-2 stimulated megakaryocyte colony formation in a dose-dependent fashion. Half-maximal effect of the two FGFs was observed at 1 ng/ml, and their effect was saturating at 20 ng/ml. The addition of heparin to cultures stimulated by FGF-1 or FGF-2 resulted in a 2-fold increase in the number of megakaryocyte colonies compared to the culture containing FGF alone. In the presence of heparin (5 IU/ml), FGF at 1 ng/ml exerted an almost maximal stimulating effect on megakaryocyte colony formation. When murine and human CD34+ cells were used as target cells, a similar interaction between FGF and heparin was observed. The combination of FGF and heparin induced a maximal growth of megakaryocyte colonies from CD34+ cells. These findings demonstrate the synergistic effect of heparin and FGF on megakaryocytopoiesis.
Chen
Q S
QS
Shanghai Institute of Hematology, Shanghai Second Medical University, People's Republic of China.
Wang
Z Y
ZY
Han
Z C
ZC
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D019070:Cell Lineage / Q000187:drug effects; D002478:Cells, Cultured; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D016220:Fibroblast Growth Factor 1; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D006410:Hematopoiesis / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008533:Megakaryocytes / Q000166:cytology*; D051379:Mice; D008807:Mice, Inbred BALB C
D005343:Fibrinolytic Agents; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D006493:Heparin