Generation of Lungs by Blastocyst Complementation in Apneumic Fgf10-Deficient Mice
Generation of Lungs by Blastocyst Complementation in Apneumic Fgf10-Deficient Mice
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DOI：
10.1016/j.celrep.2020.107626
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发表时间：
2020-05-12
期刊：
影响因子：
8.8
通讯作者：
Zhou, Qiliang
中科院分区：
文献类型：
--
作者：
Kitahara, Akihiko;Ran, Qingsong;Zhou, Qiliang
供体肺的短缺阻碍了肺移植，肺移植是终末期肺病患者的唯一决定性选择。胚泡互补使得能够在动物模型中从多能干细胞（PSC）产生可移植器官。在啮齿动物模型中，通过胚泡互补从PSC产生胰腺和肾脏。在这里，我们报告了使用小鼠胚胎干细胞（ESC）通过胚泡互补在无发育能力的Fgf 10 Ex 1（mut）/Ex 3（mut）小鼠中产生肺，与ESC的互补使Fgf 10缺陷小鼠能够存活至成年而没有异常，产生的肺泡实质和间质部分，包括血管内皮细胞、血管和支气管旁平滑肌细胞和结缔组织，主要来源于注射的ESC。这些数据表明，Fgf 10 Ex 1（mut）/Ex 3（mut）囊胚为肺生成提供了一个器官生态位，囊胚互补可能是生成全肺的可行方法。
The shortage of donor lungs hinders lung transplantation, the only definitive option for patients with endstage lung disease. Blastocyst complementation enables the generation of transplantable organs from pluripotent stem cells (PSCs) in animal models. Pancreases and kidneys have been generated from PSCs by blastocyst complementation in rodent models. Here, we report the generation of lungs using mouse embryonic stem cells (ESCs) in apneumic Fgf10 Ex1(mut)/Ex3(mut) mice by blastocyst complementation, Complementation with ESCs enables Fgf10-deficient mice to survive to adulthood without abnormalities, Both the generated lung alveolar parenchyma and the interstitial portions, including vascular endothelial cells, vascular and parabronchial smooth muscle cells, and connective tissue, largely originate from the injected ESCs. These data suggest that Fgf10 Ex1(mut)/Ex3(mut) blastocysts provide an organ niche for lung generation and that blastocyst complementation could be a viable approach for generating whole lungs.