Bioengineering of Transplantable Humanized Lungs from iPS Cells

利用 iPS 细胞进行可移植人源化肺的生物工程

基本信息

批准号：
8517179
负责人：
Darrell N. Kotton
金额：
$ 72.77万
依托单位：
BOSTON UNIVERSITY MEDICAL CAMPUS
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-15 至 2015-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8517179
关键词：
Address Allogenic Alveolar American Animals Autologous Biological Assay Biological Models Biomedical Engineering Biopsy Blood Vessels Cell Differentiation process Cell Line Cells Cellular biology Chronic Obstructive Airway Disease Clinical Cystic Fibrosis Cystic Fibrosis Transmembrane Conductance Regulator Derivation procedure Development Developmental Biology Disease Disease model Elasticity Embryo Endoderm Endothelial Cells Engraftment Environmental air flow Epithelial Epithelial Cells Failure Future Gases Gene Expression Profiling Genetic Goals Hamman-Rich syndrome Heart Hereditary Disease Human Image Immunosuppressive Agents In Vitro Individual Inherited Lung Lung Transplantation Lung diseases Mechanics Methodology Methods Modeling Molecular and Cellular Biology Morbidity - disease rate Mutation Natural regeneration Organ Patients Perfusion Pharmaceutical Preparations Phenotype Physiology Population Production Property Publishing Pulmonary Emphysema Rattus Seeds Sheep Skin Source Staging Stem cells Stress Structure Structure of parenchyma of lung Technology Testing Therapeutic Tissue Engineering Tissues Transplantation Undifferentiated Veterinary Medicine abstracting artificial lung base design disease phenotype disease-causing mutation improved in vivo induced pluripotent stem cell interdisciplinary approach lung development mortality novel precursor cell progenitor research clinical testing scaffold stem surfactant three-dimensional modeling

项目摘要

DESCRIPTION (provided by applicant): This project proposes to develop the methodologies necessary to derive a functioning transplantable humanized lung from normal or disease-specific induced pluripotent stem (iPS) cells. Successful transplantation of this bioengineered lung would imply that any patient with end-stage lung disease could receive an ex vivo bioengineered lung generated from autologous iPS cells obtained from a simple skin biopsy. Successful completion of this project would also result in the first three-dimensional model system able to examine human lung epithelial lineage relationships and able to functionally test putative human lung stem/progenitor populations both in vitro and in vivo. For this proposal we have assembled four teams with expertise in stem cell and developmental biology, tissue engineering, biomedical engineering, veterinary medicine, and lung cell biology. We propose to utilize iPS cells we have derived from humans with/without cystic fibrosis to develop methods for: a) directed differentiation of the iPS cells into lung epithelial progenitors and endothelial cells, b) ex vivo seeding of the resulting cells onto pulmonary airway, alveolar, and vascular compartments of decellularized human lung scaffolds, c) transplantation of the bioengineered lungs into large animal recipients, and d) development of an ex vivo 3D bioartificial lung model of inherited lung disease. (End of Abstract)

描述（由申请人提供）：该项目拟开发必要的方法，从正常或疾病特异性诱导多能干（iPS）细胞中衍生出具有功能的可移植人源化肺。这种生物工程肺的成功移植意味着任何患有终末期肺病的患者都可以接受由简单皮肤活检获得的自体 iPS 细胞产生的离体生物工程肺。该项目的成功完成还将产生第一个三维模型系统，能够检查人肺上皮谱系关系，并能够在体外和体内功能测试假定的人肺干/祖细胞群。对于这项提案，我们组建了四个在干细胞和发育生物学、组织工程、生物医学工程、兽医学和肺细胞生物学方面拥有专业知识的团队。我们建议利用我们从患有/不患有囊性纤维化的人类中衍生的 iPS 细胞来开发以下方法：a）将 iPS 细胞定向分化为肺上皮祖细胞和内皮细胞，b）将所得细胞离体接种到肺气道上，脱细胞人肺支架的肺泡和血管区室，c) 将生物工程肺移植到大型动物受体中，以及 d) 开发离体 3D 生物人工肺遗传性肺病模型。（摘要完）