2017年2月28日
Novel TPO receptor agonist TA-316 contributes to platelet biogenesis from human iPS cells.
Blood advances
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- 巻
- 1
- 号
- 7
- 開始ページ
- 468
- 終了ページ
- 476
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1182/bloodadvances.2016000844
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.
- リンク情報
- ID情報
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- DOI : 10.1182/bloodadvances.2016000844
- ISSN : 2473-9529
- PubMed ID : 29296963
- PubMed Central 記事ID : PMC5738977