Effects of amifostine on the proliferation and differentiation of megakaryocytic progenitor cells.
This study investigated the effects of amifostine, a clinically usable radioprotector or chemoprotector, on the proliferation and differentiation of normal and X-irradiated cluster of differentiation 34 positive (CD34+) megakaryocytic progenitor cells (colony-forming unit in megakaryocytes, CFU-Meg) from human placental and umbilical cord blood (CB) in vitro. Amifostine significantly accelerated megakaryocyte colony formation in a plasma clot culture supplemented with recombinant human thrombopoietin because of an increase in immature CFU-Meg-derived large megakaryocyte colony formation. An analysis of the cells that were harvested from the culture showed that amifostine induced a 70- and an 83-fold increase in the total cell and CFU-Meg numbers, respectively, and produced hyperploid megakaryocytes of more than 8 N ploidy. The radioprotective effect of amifostine on the clonal growth of X-irradiated CD34+ CFU-Meg was observed by treatment before or after irradiation. These findings suggest that the action of amifostine extends from immature CFU-Meg to the terminal differentiation of megakaryopoiesis, and its radioprotective effect is shown in megakaryopoiesis and thrombopoiesis.
Kashiwakura
Ikuo
I
Laboratory of Radiopharmaceutical Sciences, Hokkaido College of Pharmacy, 7-1 Katsuraoka-cho, 047-0264, Otaru, Japan. ikuo-k@hokuyakudai.ac.jp
Murakami
Miho
M
Inanami
Osamu
O
Hayase
Yukitoshi
Y
Takahashi
Tsuneo A
TA
Kuwabara
Mikinori
M
Takagi
Yoshinari
Y
D004999:Amifostine / Q000494:pharmacology*; D015703:Antigens, CD / Q000032:analysis; D018952:Antigens, CD34 / Q000032:analysis; D002454:Cell Differentiation / Q000187:drug effects* / Q000528:radiation effects; D002455:Cell Division / Q000187:drug effects / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D002999:Clone Cells / Q000166:cytology / Q000187:drug effects; D003470:Culture Media; D004247:DNA / Q000235:genetics / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D005434:Flow Cytometry; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D008533:Megakaryocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D011003:Ploidies; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D013926:Thrombopoietin / Q000494:pharmacology
D015703:Antigens, CD; D018952:Antigens, CD34; D003470:Culture Media; D011837:Radiation-Protective Agents; D004247:DNA; D013926:Thrombopoietin; D004999:Amifostine