Regeneration and orthotopic transplantation of a bioartificial lung
Regeneration and orthotopic transplantation of a bioartificial lung
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DOI：
10.1038/nm.2193
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发表时间：
2010-08-01
期刊：
影响因子：
82.9
通讯作者：
Vacanti, Joseph P.
中科院分区：
文献类型：
--
作者：
Ott, Harald C.;Clippinger, Ben;Vacanti, Joseph P.
在美国，现在大约有2,000名病人在等待捐赠的肺。全世界有5000万人患有终末期肺病。生物人工肺的创建需要可行的肺结构的工程设计，使通风，灌注和气体交换。我们通过洗涤剂灌注法使肺脱细胞，并获得具有脱细胞血管、气道和肺泡的支架。为了再生气体交换组织，我们用上皮细胞和内皮细胞接种支架。为了建立功能，我们在模拟发育肺的生理环境的生物反应器中灌注和通气细胞接种的结构。到第5天，结构可以用血液灌注并使用生理压力通气，并且它们产生与分离的天然肺相当的气体交换。为了显示体内功能，我们将再生的肺移植到原位位置。移植后，结构灌注受体的循环和通气的受体的气道和呼吸肌的装置，并提供气体交换体内拔管后长达6小时。
About 2,000 patients now await a donor lung in the United States. Worldwide, 50 million individuals are living with end-stage lung disease. Creation of a bioartificial lung requires engineering of viable lung architecture enabling ventilation, perfusion and gas exchange. We decellularized lungs by detergent perfusion and yielded scaffolds with acellular vasculature, airways and alveoli. To regenerate gas exchange tissue, we seeded scaffolds with epithelial and endothelial cells. To establish function, we perfused and ventilated cell-seeded constructs in a bioreactor simulating the physiologic environment of developing lung. By day 5, constructs could be perfused with blood and ventilated using physiologic pressures, and they generated gas exchange comparable to that of isolated native lungs. To show in vivo function, we transplanted regenerated lungs into orthotopic position. After transplantation, constructs were perfused by the recipient's circulation and ventilated by means of the recipient's airway and respiratory muscles, and they provided gas exchange in vivo for up to 6 h after extubation.