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PNAS:日研究发现iPS细胞分化能力因人而异

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7月17日,日本京都大学的一个研究小组在美国《国家科学院院刊》(<em>PNAS</em>)网络版上报告说,他们发现在利用诱导多功能干细胞(iPS细胞)培育肝脏细胞时,由于提供初始细胞的志愿者身体条件不同,培育出的iPS细胞的分化能力存在很大差异。

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iPS细胞是提取特定人体细胞(初始细胞)并向其内部植入特殊基因后培育而成的,它们有潜力分化成多种人体组织细胞。但日本研究者发现,iPS细胞分化成肝脏细胞和心肌细胞的效率因初始细胞的特点而异,也会因提供者的遗传特性和培养条件等产生差异。

京都大学iPS细胞研究所的青井贵之和山中伸弥领导的研究小组,从3名志愿者的皮肤细胞和白血球中采集细胞,培育出iPS细胞,然后鉴别其是否发育成肝脏细胞。结果发现,源自不同志愿者的iPS细胞分化出的肝脏细胞数量,在某检测指标方面存在3倍左右的差距,这表明初始细胞提供者的身体条件对iPS细胞的分化能力具有重大影响。

研究小组认为,虽然参加这项研究的志愿者人数很少,尚无法得出最终结论,但这一发现有望成为再生医疗领域应用iPS细胞的重要参考。研究小组准备今后继续进行详细研究,以期了解iPS细胞分化能力出现差异的具体原因。 
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<a title="" href="http://dx.doi.org/10.1073/pnas.1209979109" target="_blank">doi:10.1073/pnas.1209979109</a>
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<br/><strong>Donor-dependent variations in hepatic differentiation from human-induced pluripotent stem cells</strong><br/>


Masatoshi Kajiwaraa,b, Takashi Aoia, Keisuke Okitaa, Ryosuke Takahashic, Haruhisa Inouea, Naoya Takayamaa, Hiroshi Endoa, Koji Etoa, Junya Toguchidaa,d, Shinji Uemotob, and Shinya Yamanakaa,e,1

Hepatocytes generated from human induced pluripotent stem cells (hiPSCs) are unprecedented resources for pharmaceuticals and cell therapy. However, the in vitro directed differentiation of human pluripotent stem cells into mature hepatocytes remains challenging. Little attention has so far been paid to variations among hiPSC lines in terms of their hepatic differentiation. In the current study, we developed an improved hepatic differentiation protocol and compared 28 hiPSC lines originated from various somatic cells and derived using retroviruses, Sendai viruses, or episomal plasmids. This comparison indicated that the origins, but not the derivation methods, may be a major determinant of variation in hepatic differentiation. The hiPSC clones derived from peripheral blood cells consistently showed good differentiation efficiency, whereas many hiPSC clones from adult dermal fibroblasts showed poor differentiation. However, when we compared hiPSCs from peripheral blood and dermal fibroblasts from the same individuals, we found that variations in hepatic differentiation were largely attributable to donor differences, rather than to the types of the original cells. These data underscore the importance of donor differences when comparing the differentiation propensities of hiPSC clones.

<br/>来源:新华社

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