Infusion of mature megakaryocytes into mice yields functional platelets.
Thrombopoiesis, the process by which circulating platelets arise from megakaryocytes, remains incompletely understood. Prior studies suggest that megakaryocytes shed platelets in the pulmonary vasculature. To better understand thrombopoiesis and to develop a potential platelet transfusion strategy that is not dependent upon donors, of which there remains a shortage, we examined whether megakaryocytes infused into mice shed platelets. Infused megakaryocytes led to clinically relevant increases in platelet numbers. The released platelets were normal in size, displayed appropriate surface markers, and had a near-normal circulating half-life. The functionality of the donor-derived platelets was also demonstrated in vivo. The infused megakaryocytes mostly localized to the pulmonary vasculature, where they appeared to shed platelets. These data suggest that it may be unnecessary to generate platelets from ex vivo grown megakaryocytes to achieve clinically relevant increases in platelet numbers.
Fuentes
Rudy
R
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
Wang
Yuhuan
Y
Hirsch
Jessica
J
Wang
Cheng
C
Rauova
Lubica
L
Worthen
G Scott
GS
Kowalska
M Anna
MA
Poncz
Mortimer
M
D000818:Animals; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D017690:Cell Transplantation / Q000379:methods*; D004195:Disease Models, Animal; D006207:Half-Life; D008533:Megakaryocytes / Q000637:transplantation*; D051379:Mice; D008810:Mice, Inbred C57BL; D010976:Platelet Count; D013921:Thrombocytopenia / Q000503:physiopathology / Q000628:therapy; D034061:Thrombopoiesis / Q000502:physiology; D013927:Thrombosis / Q000473:pathology