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The in vitro effects of cytokines on expansion and migration of megakaryocyte progenitors
Author(s) -
Drayer A. Lyndsay,
Sibinga Cees T. Smit,
Blom Nel R.,
De Wolf Joost T. M.,
Vellenga Edo
Publication year - 2000
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1046/j.1365-2141.2000.02079.x
Subject(s) - megakaryocyte , progenitor cell , stem cell factor , haematopoiesis , microbiology and biotechnology , stromal cell , biology , cytokine , clonogenic assay , interleukin 3 , stem cell , growth factor , immunology , in vitro , cancer research , receptor , t cell , antigen presenting cell , biochemistry , immune system
Increasing the number of megakaryocyte progenitors in stem cell transplants by ex vivo expansion culture may be an approach to accelerate platelet recovery in patients undergoing high‐dose chemotherapy. We evaluated the effect of three different cytokine combinations on expansion, with special emphasis on the type of colony formation and migration of megakaryocytic cells. The number of clonogenic megakaryocyte progenitors (colony‐forming units–megakaryocyte; CFU‐Mk) with high‐ (> 20 cells/colony) and low‐proliferative capacity (5–20 cells/colony) and the number of megakaryocytic (CD61 + ) cells were significantly increased by including interleukin 3 (IL‐3) or IL‐3 + IL‐6 + IL‐11 + Flt3‐ligand to cultures containing megakaryocyte growth and development factor (MGDF) plus stem cell factor (SCF). No difference in the maturation of megakaryocytes from all three cytokine combinations to platelets were observed, as demonstrated by electron microscopy. In chemotaxis experiments, the migration towards stromal cell‐derived factor 1 (SDF‐1) was shown to be reduced for CD61 + cells and megakaryocyte progenitors cultured in other cytokines besides MGDF + SCF. The reduced migration was related to a lower expression of CXCR4, the receptor for SDF‐1, on megakaryocytes from the proliferating cultures. These in vitro results demonstrate that expansion in IL‐3 and other cytokines besides MGDF + SCF significantly impair the capacity of megakaryocytic cells to migrate.