Department of Surgery, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Nat Med. 2010 Aug;16(8):927-33. doi: 10.1038/nm.2193. Epub 2010 Jul 13.
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.
目前，大约有 2000 名患者在美国等待供体肺。在全球范围内，有 5000 万人患有晚期肺病。生物人工肺的创建需要对可行的肺结构进行工程设计，以实现通气、灌注和气体交换。我们通过去污剂灌注使肺去细胞化，得到了具有无细胞血管、气道和肺泡的支架。为了再生气体交换组织，我们将上皮细胞和内皮细胞接种到支架上。为了建立功能，我们在生物反应器中对细胞接种的构建体进行灌注和通气，模拟发育中肺的生理环境。到第 5 天，构建体可以用血液灌注，并使用生理压力进行通气，它们产生的气体交换与分离的天然肺相当。为了展示体内功能，我们将再生的肺移植到原位。移植后，构建体通过受体的循环进行灌注，并通过受体的气道和呼吸肌进行通气，在拔出气管导管后，它们可以在体内提供长达 6 小时的气体交换。
