JEM：利用ips制造血小板的技术

日本东京大学的研究人员宣布，他们开发出了用诱导多功能干细胞（iPS细胞）制造血小板的技术，并通过动物实验确认了制造出来的血小板具有止血功能。

iPS细胞是具有较强分化潜力的干细胞，由皮肤细胞等体细胞经基因改造“诱导”发育而成。培养这类细胞不需要利用人类早期胚胎，而且可以无限增殖，因此新技术有望用于大量生产输血用的血小板。

东京大学副教授江藤浩之率领的研究小组，在22日的美国《实验医学杂志》月刊上发表论文说，他们首先利用人体皮肤纤维组织母细胞和脐带血细胞制造出iPS细胞，然后加入几种血液细胞增殖因子和营养细胞，培养出能够制造血小板的巨核细胞，最终制造出血小板。

研究人员将制造出的血小板输给小鼠，发现血小板集中到受伤的血管上，形成血栓，正常发挥了血小板的功能。

研究人员使用了与癌症有关的cMyc基因，能够高效制造巨核细胞并生产血小板。由于血小板中不存在含有遗传信息的细胞核，而且混杂其中的其他细胞的细胞核可以通过照射放射线和过滤去除，所以临床应用时不会有癌变的危险。

血小板是血液细胞之一，能够凝固血液，防止出血。手术时使用的血小板现在完全依赖献血。研究小组准备确认新技术的安全性之后，早日将其应用于手术。（生物谷Bioon.com）

生物谷推荐英文摘要：

JEM doi: 10.1084/jem.20100844

Transient activation of c-MYC expression is critical for efficient platelet generation from human induced pluripotent stem cells
Naoya Takayama1, Satoshi Nishimura3,4,5, Sou Nakamura1, Takafumi Shimizu2, Ryoko Ohnishi1, Hiroshi Endo1,2, Tomoyuki Yamaguchi2, Makoto Otsu2, Ken Nishimura4,6, Mahito Nakanishi6, Akira Sawaguchi7, Ryozo Nagai3,5, Kazutoshi Takahashi8, Shinya Yamanaka8, Hiromitsu Nakauchi2, and Koji Eto1

1Stem Cell Bank and 2Division of Stem Cell Therapy, Center for Stem Cell Biology and Regenerative Medicine, the Institute of Medical Science, and 3Department of Cardiovascular Medicine and 5Translational Systems Biology and Medicine Initiative, the University of Tokyo, Tokyo 113-0033, Japan
4PRESTO, Japan Science and Technology Agency, Tokyo 102-8666, Japan
6Gene Function Research Center, National Institute of Advanced Industrial Science and Technology, Ibaraki 305–8562, Japan
7Department of Anatomy, University of Miyazaki Faculty of Medicine, Miyazaki 889-1692, Japan
8Center for iPS Research and Application, Kyoto University, Kyoto 606-8507, Japan

Human (h) induced pluripotent stem cells (iPSCs) are a potentially abundant source of blood cells, but how best to select iPSC clones suitable for this purpose from among the many clones that can be simultaneously established from an identical source is not clear. Using an in vitro culture system yielding a hematopoietic niche that concentrates hematopoietic progenitors, we show that the pattern of c-MYC reactivation after reprogramming influences platelet generation from hiPSCs. During differentiation, reduction of c-MYC expression after initial reactivation of c-MYC expression in selected hiPSC clones was associated with more efficient in vitro generation of CD41a+CD42b+ platelets. This effect was recapitulated in virus integration-free hiPSCs using a doxycycline-controlled c-MYC expression vector. In vivo imaging revealed that these CD42b+ platelets were present in thrombi after laser-induced vessel wall injury. In contrast, sustained and excessive c-MYC expression in megakaryocytes was accompanied by increased p14 (ARF) and p16 (INK4A) expression, decreased GATA1 expression, and impaired production of functional platelets. These findings suggest that the pattern of c-MYC expression, particularly its later decline, is key to producing functional platelets from selected iPSC clones.