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Modeling, pathogenesis and treatment of idiopathic pulmonary fibrosis

特发性肺纤维化的建模、发病机制和治疗

基本信息

批准号：
9516638
负责人：
HANS-WILLEM E SNOECK
金额：
$ 27.2万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-09-20 至 2018-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9516638
关键词：
Acute Acute Lung Injury Address Adult Adult Respiratory Distress Syndrome Affect Animals Benchmarking Biomedical Engineering Blood Vessels Bronchoscopes Cell Therapy Cells Cellular biology Chest Clinical Clinical Research Clinical Treatment Cross Circulation Data Derivation procedure Development Distal Dose Engraftment Environmental air flow Epithelial Cells Epithelium Evaluation Excision Extracorporeal Membrane Oxygenation Family suidae Functional disorder Funding Gases Goals Grant Hamman-Rich syndrome Health Histology Hour Human Imaging technology In Situ In Vitro Inflammation Injury Institution Intervention Joints Label Lead Long-Term Effects Lung Lung Compliance Lung Transplantation Lung diseases Maintenance Modality Modeling Molecular Monitor Morbidity - disease rate Natural regeneration Operative Surgical Procedures Organoids Outcome Pathogenesis Patients Phase Phenotype Population Preparation Procedures Protocols documentation Publications Real-Time Systems Recording of previous events Recovery Regenerative Medicine Replacement Therapy Research Personnel Respiratory physiology Safety Stomach Support System Supporting Cell Technology Therapeutic Thinness Time Tissue Model Tissues Treatment Efficacy Validation Vascular Endothelium Vascular resistance adult stem cell base clinically relevant design dosage flexibility healing human adult stem cell image guided imaging modality imaging platform induced pluripotent stem cell injured innovation insight lung imaging lung preservation lung regeneration mortality non-invasive monitor novel parent grant progenitor targeted treatment theranostics therapeutic evaluation transcriptome sequencing

项目摘要

ABSTRACT This revision application entitled “Regeneration of acutely injured lungs using adult human stem cells” is to expand the scope of the parent grant “Modeling, pathogenesis and treatment of idiopathic pulmonary fibrosis” into studies that will further regenerative medicine and accelerate its use by developing an adult stem cell therapy for acute lung injury. The treatment modality we propose is to regenerate acutely injured lungs by targeted removal of damaged pulmonary epithelium (while preserving lung vasculature and surrounding parenchymal tissue), followed by delivery of iPSC-derived pulmonary cells. Both the parent grant and this application are based on three highly innovative translational technologies recently developed in our labs: (i) derivation of large numbers of pulmonary progenitors from adult human iPSCs, (ii) prolongation of ex vivo lung support from 6 hours to 3–5 days by normothermic cross-circulation, and (iii) a non- invasive theranostic system for real-time monitoring of cell delivery and lung regeneration. For maximal significance, we focus on one of the most common causes of acute lung injury - gastric aspiration - that frequently leads to acute respiratory distress syndrome (ARDS). For maximal translational potential, we chose to develop an in-situ approach to lung regeneration, where an interventional procedure will be performed in the patient, by replacing defective cells in the region(s) of injury with therapeutic human iPSC-derived pulmonary cells using a very thin, flexible, imaging-guided bronchoscope. We will study lung regeneration ex vivo under cross-circulation and ventilation (over 3–5 days) and in situ (over 1 month) in a clinically relevant porcine model, using protocols established in our previous and preliminary studies. The project is designed to collect data for preparing the IRB/FDA applications for Phase I human trials to treat acute lung injury with therapeutic human iPSC-derived pulmonary cells by the end of the 1-year grant.

摘要