| Autor: |
Ayako Aihara, Tomo Koike, Natsuki Abe, Sou Nakamura, Akira Sawaguchi, Takanori Nakamura, Naoshi Sugimoto, Hiromitsu Nakauchi, Taito Nishino, Koji Eto |
| Jazyk: |
angličtina |
| Rok vydání: |
2017 |
| Předmět: |
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| Zdroj: |
Blood Advances, Vol 1, Iss 7, Pp 468-476 (2017) |
| Druh dokumentu: |
article |
| ISSN: |
2473-9529 |
| DOI: |
10.1182/bloodadvances.2016000844 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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