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Title: Novel TPO receptor agonist TA-316 contributes to platelet biogenesis from human iPS cells
Authors: Aihara, Ayako
Koike, Tomo
Abe, Natsuki
Nakamura, Sou
Sawaguchi, Akira
Nakamura, Takanori
Sugimoto, Naoshi  kyouindb  KAKEN_id  orcid (unconfirmed)
Nakauchi, Hiromitsu
Nishino, Taito
Eto, Koji
Author's alias: 中村, 壮
杉本, 直志
江藤, 浩之
Issue Date: 28-Feb-2017
Publisher: American Society of Hematology
Journal title: Blood advances
Volume: 1
Issue: 7
Start page: 468
End page: 476
Abstract: Signaling by thrombopoietin (TPO) in complex with its receptor, c-MPL, is critical for hematopoietic stem cell (HSC) homeostasis and platelet generation. Here we show that TA-316, a novel chemically synthesized c-MPL agonist (CMA), is useful for ex vivo platelet generation from human-induced pluripotent stem (iPS) cell–derived immortalized megakaryocyte progenitor cell lines (imMKCLs). Moreover, the generation is clinically applicable, because self-renewal expansion and platelet release is tightly controllable. TA-316 but not eltrombopag, another CMA, promoted both the self-renewal and maturation of imMKCLs, leading to more than a twofold higher platelet production than that achieved with recombinant human TPO (rhTPO). Interestingly, TA-316 seemed to favor MK-biased differentiation from bone marrow CD34+ HSC/progenitors and imMKCLs through the upregulation of vascular endothelial growth factor A and fibroblast growth factor 2. This result suggests TA-316 could facilitate the development of an efficient and useful system to expand platelets from imMKCLs.
Rights: © 2017 by The American Society of Hematology
DOI(Published Version): 10.1182/bloodadvances.2016000844
PubMed ID: 29296963
Appears in Collections:Journal Articles

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