Decellularized Avian Lungs for Use in Pulmonary Therapeutics

与用于终末期心脏病患者的左心室辅助装置相比， 很少有可用于终末期肺病患者的桥接装置。体外 膜式氧合（ECMO）装置在短期急性新生儿 在急性成人呼吸道疾病中作用有限。然而，在这方面， ECMO需要在重症监护病房和专业医疗保健提供者住院治疗。作为 因此，对于长期过渡到肺移植来说，这不是一个实际或成本有效的选择。新 迫切需要具有成本效益且易于实施的创新技术。 我们广泛研究了离体肺生物工程，重点是去细胞化和再细胞化 哺乳动物的肺。这包括开发潜在的移植策略， 来自脱细胞尸体或失败供体肺的体内自体肺， 从最终的移植受体获得的细胞。这是一个强大的快速发展的 有前途的方法。然而，仍然存在一些重大障碍，包括概括 适当的气体交换和呼吸生理。 与哺乳动物的肺相反，鸟类的肺是静态的多层结构， 交换通过交叉流交换发生，并且比更复杂的交换更有效。 哺乳动物肺部所需的通风。因此，禽肺可以提供一种潜在的新方法， 和有效的生物支架，用作肺辅助装置，也可能用于移植 阴谋因此，该提议的中心假设是，脱细胞化的禽肺， 用人肺上皮细胞、内皮细胞和基质细胞再细胞化，随后用 相关的肺干细胞和祖细胞，因此将提供一种新的和更强大的气体 交换单位比再细胞化的哺乳动物肺。再细胞化的鸟肺可能是 作为独立的医院（ICU）单元使用，与ECMO、便携式单元相当， 与便携式透析设备或胰岛素泵相当，或作为气体交换单元植入 进入胸腔将在以下具体目标中对这些目标进行研究： 1.充分表征代表性禽肺的去细胞化和再细胞化。 2.开发新型禽肺辅助装置（ALAD）的初始技术， 再细胞化的禽肺可以潜在地用于独立的、便携式的或 植入式肺辅助装置。 肺部生物学家丹尼尔韦斯和工程师们将合作实现这一目标 帕特里克李和德莱弗休士顿。知识产权和技术开发这些 有关研究其后会获发牌照，以作进一步的产业发展。

In contrast to left ventricular assist devices used in end stage cardiac disease patients, there are few available bridging devices available for end stage lung disease patients. Extracorporeal membrane oxygenation (ECMO) devices have a significant role in short term acute neonatal respiratory diseases and a more limited role in acute adult respiratory diseases. However, ECMO requires hospitalization in critical care units and specialized health care providers. As such, it is not a practical or cost effective option for long term bridging to lung transplant. New innovative cost-effective easily implementable technologies are desperately needed. We have extensively studied ex vivo lung bioengineering with focus on de- and recellularization of mammalian lungs. This includes developing potential transplantation strategies creating ex vivo autologous lungs from decellularized cadaveric or failed donor lungs recellularized with cells obtained from the eventual transplant recipient. This is a powerful rapidly evolving promising approach. However, a number of significant hurdles remain including recapitulating appropriate gas exchange and respiratory physiology. As opposed to mammalian lungs, avian lungs are static multilayered structures in which gas exchange occurs by cross current exchange and is more efficient than the more complex ventilation required by mammalian lungs. As such, avian lungs could provide a potentially novel and effective bioscaffold for use as lung assist devices and possibly also in transplantation schemes. The central hypothesis of this proposal therefore is that decellularized avian lungs, recellularized with human lung epithelial, endothelial, and stromal cells, and subsequently with relevant lung stem and progenitor cells, will therefore provide a novel and more powerful gas exchange unit than recellularized mammalian lungs. The recellularized avian lungs could be utilized as independent hospital (ICU)-based units, comparable to ECMO, portable units, comparable to portable dialysis devices or insulin pumps, or as gas exchange units implantable into the thoracic cavity. These objectives will be investigated in the following Specific Aims: 1. To fully characterize de- and recellularization of representative avian lungs. 2. To develop initial technologies for novel Avian Lung Assist Devices (ALAD) incorporating recellularized avian lungs that could be potentially utilized for independent, portable, or implantable lung assist devices. The aims will be pursued in collaboration between lung biologist Daniel Weiss and engineers Patrick Lee and Dryver Huston. The intellectual property and technology developed from these studies will be subsequently licensed for further industry-based development.