1. Academic Validation
  2. Novel TPO receptor agonist TA-316 contributes to platelet biogenesis from human iPS cells

Novel TPO receptor agonist TA-316 contributes to platelet biogenesis from human iPS cells

  • Blood Adv. 2017 Feb 28;1(7):468-476. doi: 10.1182/bloodadvances.2016000844.
Ayako Aihara 1 Tomo Koike 2 Natsuki Abe 1 Sou Nakamura 2 Akira Sawaguchi 3 Takanori Nakamura 1 Naoshi Sugimoto 2 Hiromitsu Nakauchi 4 Taito Nishino 1 Koji Eto 2 5
Affiliations

Affiliations

  • 1 Biological Research Laboratories, Nissan Chemical Industries Ltd., Saitama, Japan.
  • 2 Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
  • 3 Department of Anatomy, Miyazaki University Faculty of Medicine, Miyazaki, Japan.
  • 4 Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan; and.
  • 5 Department of Regenerative Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.
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.

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