Generation of Rat Pancreas in Mouse by Interspecific Blastocyst Injection of Pluripotent Stem Cells
Generation of Rat Pancreas in Mouse by Interspecific Blastocyst Injection of Pluripotent Stem Cells
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DOI：
10.1016/j.cell.2010.07.039
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发表时间：
2010-09-03
期刊：
影响因子：
64.5
通讯作者：
Nakauchi, Hiromitsu
中科院分区：
文献类型：
--
作者：
Kobayashi, Toshihiro;Yamaguchi, Tomoyuki;Nakauchi, Hiromitsu
器官发生的复杂性阻碍了从患者的多能干细胞（PSCs）中体外生成器官，这是再生医学的最终目标。将小鼠野生型PSCs注射到Pdx1(-/-)（胰腺发生障碍）小鼠囊胚中，发育补偿了胰腺“发育生态位”的空缺，产生了几乎完全的PSCs衍生的胰腺。为了研究异种途径在囊胚互补中的潜力，我们分别将小鼠或大鼠PSCs注射到大鼠或小鼠囊胚中，产生种间嵌合体，从而证实PSCs可以促进小鼠和大鼠之间的异种发育。这些小鼠/大鼠嵌合体的发育主要受到宿主囊胚和/或养母的影响，这在体型和物种特异性器官发生方面表现得很明显。我们进一步将大鼠野生型PSCs注射到Pdx1（-/-）小鼠囊胚中，在Pdx1（-/-）小鼠中产生功能正常的大鼠胰腺。这些数据证明了种间囊胚互补的原理，以及利用异种环境在体内产生来自供体psc的器官。
The complexity of organogenesis hinders in vitro generation of organs derived from a patient's pluripotent stem cells (PSCs), an ultimate goal of regenerative medicine. Mouse wild-type PSCs injected into Pdx1(-/-) (pancreatogenesis-disabled) mouse blastocysts developmentally compensated vacancy of the pancreatic "developmental niche,'' generating almost entirely PSC-derived pancreas. To examine the potential for xenogenic approaches in blastocyst complementation, we injected mouse or rat PSCs into rat or mouse blastocysts, respectively, generating interspecific chimeras and thus confirming that PSCs can contribute to xenogenic development between mouse and rat. The development of these mouse/rat chimeras was primarily influenced by host blastocyst and/or foster mother, evident by body size and species-specific organogenesis. We further injected rat wild-type PSCs into Pdx1(-/-) mouse blastocysts, generating normally functioning rat pancreas in Pdx1(-/-) mice. These data constitute proof of principle for interspecific blastocyst complementation and for generation in vivo of organs derived from donor PSCs using a xenogenic environment.