Decellularized Avian Lungs for Use in Pulmonary Therapeutics

用于肺部治疗的脱细胞禽肺

基本信息

批准号：
9432537
负责人：
DANIEL J WEISS
金额：
$ 23.4万
依托单位：
UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-02-15 至 2020-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9432537
关键词：
Acute Adult Allogenic Autologous Biological Biomedical Engineering Birds Blood Vessels Cadaver Cells Chickens Clinical Collaborations Collagen Collagen Type IV Complex Critical Care Data Development Devices Dialysis procedure Electron Microscopy Emu species Endothelial Cells Engineering Environmental air flow Epithelial Epithelial Cells Extracellular Matrix Extracellular Matrix Proteins Extracorporeal Membrane Oxygenation Fibroblasts Fibronectins Gases Goals Health Personnel Heart Diseases Histologic Hospitalization Hospitals Human Immunohistochemistry Industry Insulin Infusion Systems Intellectual Property Intervention Laminin Life Lung Lung Transplantation Lung diseases Mass Spectrum Analysis Mesenchymal Modality Modeling Neonatal Outpatients Patients Pilot Projects Principal Investigator Research Personnel Respiratory physiology Role Savings Scheme Stem cells Stromal Cells Structure Struthio camelus Techniques Technology Therapeutic Thoracic cavity structure Transplant Recipients Transplantation Vascular Endothelial Cell Waiting Lists base combinatorial cost effective innovation left ventricular assist device light microscopy new technology novel novel strategies portability

项目摘要

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.

与在末期心脏病患者中使用的左心室辅助装置相反，有很少有可用于末期肺部病患者的可用桥接设备。体外膜氧合（ECMO）设备在短期急性新生儿中具有重要作用呼吸道疾病和在急性成人呼吸道疾病中的作用更有限。然而， ECMO需要在重症监护病房和专业医疗保健提供者中住院。作为这样的长期桥接肺移植并不是实用或具有成本效益的选择。新的迫切需要创新的成本效益易于实施的技术。我们已经广泛研究了离体肺部生物工程，重点是延期和卷积哺乳动物肺。这包括制定潜在的移植策略创建EX 来自脱细胞尸体或失败的供体肺的体内自体肺从最终的移植受体获得的细胞。这是一个迅速发展的强大有希望的方法。但是，仍然存在许多重大障碍，包括概括适当的气体交换和呼吸生理学。与哺乳动物肺相反，禽肺是静态多层结构交换是通过交叉交换发生的，比更复杂的哺乳动物肺所需的通风。因此，禽肺可以提供潜在的新颖并有效用作肺辅助设备的生物施加剂，也可能是移植方案。因此，该提议的中心假设是脱细胞化禽肺，用人的肺上皮，内皮和基质细胞对重新细胞，然后因此，相关的肺茎和祖细胞将提供一种新颖，更强大的气体交换单元比哺乳动物肺部肺部。延迟的禽肺可能是用作基于独立医院（ICU）的单元，可与ECMO，便携式单元相当，与便携式透析设备或胰岛素泵或与气体交换单元相比进入胸腔。这些目标将在以下具体目的中进行调查： 1。充分表征代表性禽肺的延迟和延迟。 2。开发新型禽肺辅助设备（ALAD）的初始技术可能用于独立，便携式或可植入的肺辅助装置。肺生物学家丹尼尔·魏斯（Daniel Weiss）与工程师之间的合作将追求目标帕特里克·李（Patrick Lee）和干弗·休斯顿（Huston）。这些知识产权和技术从这些发展随后，研究将获得基于行业的发展的许可。