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Blood Adv. 2017 Feb 28;1(7):468-476. doi: 10.1182/bloodadvances.2016000844. eCollection 2017 Feb 28.

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

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Biological Research Laboratories, Nissan Chemical Industries Ltd., Saitama, Japan.
Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, Kyoto, Japan.
Department of Anatomy, Miyazaki University Faculty of Medicine, Miyazaki, Japan.
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.
Department of Regenerative Medicine, Chiba University Graduate School of Medicine, Chiba, Japan.


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.

Conflict of interest statement

Conflict-of-interest disclosure: T. Nishino, T. Nakamura, H.N., and K.E. have applied for a patent related to this work; H.N. is a scientific advisory member of ReproCELL and Megakaryon Corporation; and H.N. and K.E. are founders of Megakaryon Corporation. The interests of K.E. were reviewed and are managed by Kyoto University in accordance with its conflict-of-interest policies. The remaining authors declare no competing financial interests.

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