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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.

Author information

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.

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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