生物
造血
巨核细胞
祖细胞
血小板
诱导多能干细胞
细胞生物学
干细胞
细胞培养
免疫学
体重指数1
癌症研究
胚胎干细胞
遗传学
基因
作者
Sou Nakamura,Naoya Takayama,Shinji Hirata,Hideya Seo,Hiroshi Endô,Kenji Ochi,Ken‐ichi Fujita,Tsuneaki Koike,Kenichi Harimoto,Takeaki Dohda,Akira Watanabe,Keisuke Okita,Nobuyasu Takahashi,Akira Sawaguchi,Shinya Yamanaka,Hiromitsu Nakauchi,Satoshi Nishimura,Koji Eto
出处
期刊:Cell Stem Cell
[Elsevier]
日期:2014-04-01
卷期号:14 (4): 535-548
被引量:279
标识
DOI:10.1016/j.stem.2014.01.011
摘要
The donor-dependent supply of platelets is frequently insufficient to meet transfusion needs. To address this issue, we developed a clinically applicable strategy for the derivation of functional platelets from human pluripotent stem cells (PSCs). This approach involves the establishment of stable immortalized megakaryocyte progenitor cell lines (imMKCLs) from PSC-derived hematopoietic progenitors through the overexpression of BMI1 and BCL-XL to respectively suppress senescence and apoptosis and the constrained overexpression of c-MYC to promote proliferation. The resulting imMKCLs can be expanded in culture over extended periods (4-5 months), even after cryopreservation. Halting the overexpression of c-MYC, BMI1, and BCL-XL in growing imMKCLs led to the production of CD42b(+) platelets with functionality comparable to that of native platelets on the basis of a range of assays in vitro and in vivo. The combination of robust expansion capacity and efficient platelet production means that appropriately selected imMKCL clones represent a potentially inexhaustible source of hPSC-derived platelets for clinical application.
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