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Cell Stem Cell:新干细胞技术能产生大量血小板,满足临床使用

来源:生物谷 2014-02-15 22:38

2014年2月15日 讯 /生物谷BIOON/ --血小板具有凝血功能,多种外伤和血液疾病的治疗都需要血小板。但是现在血小板只能从献血中提取。近日发表在Cell Stem Cell杂志上的文章称,科学家开发出一种新型产生血小板的方法,该方法有望解决血小板紧缺问题,满足临床治疗的需求。

血小板无法满足临床需求的一个原因是血小板只能在室温保存,并且寿命很短。而且输入性血小板通常与病人的免疫系统不相容,重复输入不相容的血小板会导致输入血小板无效的现象。

为了解决血小板紧缺的问题,日本科学家开发出一种新方法,能够从人类IPS细胞中产生功能型血小板。在本研究中,科学家将IPS稳定的诱导为能够产生血小板的巨核细胞祖细胞。

巨核细胞祖细胞能够产生大量的血小板,该血小板功能与献血中提取血小板凝血能力相当。然而其重要的优势在于,巨核细胞祖细胞能够扩增,也能长时间冷冻保存。

该文章的通讯作者京都大学Koji Eto博士称,我们构建了稳定的巨核细胞祖细胞系,该细胞系能够长时间自我复制,并能够产生大量的血小板,供给临床使用。(生物谷Bioon.com)

doi:10.1016/j.stem.2014.01.011

Expandable Megakaryocyte Cell Lines Enable Clinically Applicable Generation of Platelets from Human Induced Pluripotent Stem Cells

Sou Nakamura, Naoya Takayama, Shinji Hirata, Hideya Seo, Hiroshi Endo, Kiyosumi Ochi, Ken-ichi Fujita, Tomo Koike, Ken-ichi Harimoto, Takeaki Dohda, Akira Watanabe, Keisuke Okita, Nobuyasu Takahashi, Akira Sawaguchi, Shinya Yamanaka, Hiromitsu Nakauchi, Satoshi Nishimura, Koji Eto

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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