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，有 对于终末期肺部疾病患者，可用的桥接设备很少。体外循环 膜氧合(ECMO)装置在短期急性新生儿中的重要作用 呼吸系统疾病在成人急性呼吸道疾病中的作用较为有限。然而， ECMO要求在重症监护病房和专门的医疗保健提供者住院。AS 因此，对于肺移植的长期桥接来说，这并不是一个切实可行的选择，也不具有成本效益。新的 人们迫切需要创新、成本效益高、易于实施的技术。 我们广泛研究了体外肺生物工程，重点是去细胞和再细胞化。 哺乳动物的肺。这包括开发潜在的移植战略，创建前 脱细胞身体肺或失败供体肺的活体自体肺 从最终的移植接受者那里获得的细胞。这是一种强大的、快速发展的 前景看好的方法。然而，仍然存在一些重大障碍，包括重述 适当的气体交换和呼吸生理学。 与哺乳动物的肺不同，鸟类的肺是静态的多层结构，其中气体 交换通过交叉电流交换进行，比更复杂的交换更有效 哺乳动物肺所需的通气量。因此，鸟肺可能会提供一种潜在的新奇 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，这一提议的中心假设是去细胞的鸟类肺， 用人肺上皮细胞、内皮细胞和基质细胞再细胞，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。再细胞化的禽肺可能是 用作以独立医院(ICU)为基础的单元，可与ECMO、便携式单元、 可与便携式透析设备或胰岛素泵相媲美，或可植入气体交换装置 进入胸腔。这些目标将按以下具体目标进行调查： 1.充分表征典型禽肺的去细胞化和再细胞化。 2.开发新型禽肺辅助装置(ALAD)的初步技术 再细胞化的禽肺可能被用于独立、便携式或 植入式肺辅助装置。 这些目标将在肺部生物学家丹尼尔·韦斯和工程师的合作下进行 帕特里克·李和德雷弗·休斯顿。从这些发展而来的知识产权和技术 随后，研究将获得许可，以供进一步以行业为基础的开发。

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.