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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.

与终末期心脏病患者使用的左心室辅助装置相比，可用于终末期肺病患者的可用桥接装置很少。体外膜氧合（ECMO）设备在短期急性新生儿中发挥着重要作用呼吸系统疾病和急性成人呼吸系统疾病的作用较为有限。然而， ECMO 需要重症监护病房和专业医疗保健提供者住院。作为因此，对于肺移植的长期桥接来说，它不是一个实用或具有成本效益的选择。新的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，重点是脱细胞和再细胞化哺乳动物的肺部。这包括开发潜在的移植策略，创造前来自脱细胞尸体或失败的供体肺的体内自体肺再细胞化从最终的移植受体获得的细胞。这是一个强大且快速发展的有前途的方法。然而，仍然存在一些重大障碍，包括重述适当的气体交换和呼吸生理学。与哺乳动物的肺相反，禽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，并且比更复杂的交换更有效哺乳动物肺部所需的通气量。因此，禽肺可以提供一种潜在的新颖的和有效的生物支架，可用作肺辅助装置，也可能用于移植计划。因此，该提案的中心假设是脱细胞禽肺，用人肺上皮细胞、内皮细胞和基质细胞进行再细胞化，然后用相关的肺干细胞和祖细胞，因此将提供一种新颖且更强大的气体交换单位比再细胞化的哺乳动物肺更重要。再细胞化的禽肺可能是用作独立医院 (ICU) 的单位，与 ECMO、便携式单位相当，与便携式透析设备或胰岛素泵相当，或作为可植入的气体交换装置进入胸腔。这些目标将在以下具体目标中进行调查： 1. 充分表征代表性禽肺的脱细胞和再细胞化。 2. 开发新型禽肺辅助装置 (ALAD) 的初步技术再细胞化禽肺，可用于独立、便携式或植入式肺辅助装置。肺生物学家 Daniel Weiss 和工程师将共同努力实现这一目标帕特里克·李和德莱弗·休斯顿。由此开发的知识产权和技术随后研究将获得许可用于进一步的基于行业的开发。