iPSC-Derived Alveolar Epithelial Cells for Intrapulmonary Therapies

用于肺内治疗的 iPSC 衍生肺泡上皮细胞

基本信息

批准号：
9019934
负责人：
Alice F Tarantal
金额：
$ 19.3万
依托单位：
UNIVERSITY OF CALIFORNIA AT DAVIS
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-12-01 至 2017-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9019934
关键词：
Accounting Address Adverse effects Age Alveolar Amniotic Fluid Biological Assay Bioreactors Birth Cell Differentiation process Cell Lineage Cell Proliferation Cell Therapy Cell Transplants Cell physiology Cells Characteristics Child Childhood Controlled Environment Cultured Cells Custom Development Disease Distal Dose Endoderm Engineering Engraftment Environment Epithelial Cells Exogenous Factors Extracellular Matrix Fetal Monitoring Gene Transfer Goals Growth Human Image Imaging technology Immunohistochemistry Infant Inherited Interstitial Lung Diseases Investigation Label Legal patent Life Liquid substance Longevity Lung Lung Transplantation Lung diseases LysoTracker Macaca mulatta Methods Modeling Monitor Monkeys Morphology Patients Phenotype Pleural Pluripotent Stem Cells Polysaccharides Population Positron-Emission Tomography Primates Protein Deficiency Protocols documentation Pulmonary Surfactant-Associated Protein B Pulmonary Surfactants Research Research Infrastructure Shapes Staging Stem cell transplant Stem cells Structure of parenchyma of lung System Techniques Technology Term Birth Testing Third Pregnancy Trimester Tissue Engineering Tissue Harvesting Tissues Translational Research Transplant-Related Disorder Transplantation Ultrasonography X-Ray Computed Tomography age group alveolar type II cell base bioluminescence imaging body system cell growth clinically relevant fetal high risk imaging modality in vivo in vivo imaging induced pluripotent stem cell innovation insight meetings morphometry nonhuman primate novel novel marker novel therapeutics public health relevance regenerative repaired response scaffold stem stem cell fate specification surfactant surfactant deficiency three dimensional cell culture tool trafficking

项目摘要

DESCRIPTION (provided by applicant): This application is submitted in response to PAR-13-095 with the intent of testing lineage committed cells derived from human induced pluripotent stem cells (hiPSC) for the treatment of congenital lung diseases. The approaches outlined in this proposal build on the expertise of our team in developmental ontogeny, tissue engineering, stem/progenitor cell studies, novel in vivo imaging modalities, and a translational nonhuman primate model. We have studied methods to differentiate human pluripotent cells towards lung-related lineages including airway epithelial cells (AECs); engineered constructs with unique scaffolds and matrices; and developed techniques to effectively label, transplant, and monitor the fate of transplanted precursors in vivo in rhesus monkeys. We are now poised to advance our prior discoveries and break new ground to address key questions related to iPSC-derived precursors to treat congenital lung diseases, such as pulmonary surfactant deficiency, through the following Specific Aims: (1) Optimize lineage commitment of hiPSCs in 3D culture to enhance AEC differentiation and purity, and (2) Conduct proof-of-concept studies to evaluate fetal transplant efficiency and cell fate in vivo. We will optimize proliferation and integration o key cell populations in 3D culture to enhance lineage specification, and evaluate transplant efficiency and cell fate in vivo through innovative imaging paradigms including bioluminescence imaging and positron emission tomography/computed tomography (PET/CT). The lung has limited capacity for repair, and regenerative concepts that are based on developmental principles, tailored to the age of the patient, tested in a translational primate model, and use state-of-the-art imaging technologies could have a major impact on the field. These investigations will provide new insights and guide new avenues of translational research that could have significant impact and compelling benefits for children and all age groups across the lifespan.

描述（由应用程序提供）：该应用是针对PAR-13-095提交的，目的是测试源自人类诱导的多能干细胞（HIPSC）的谱系固定细胞，以治疗先天性肺部疾病。该提案中概述的方法建立在我们团队的专家开发本体发育，组织工程，茎/祖细胞研究，新颖的体内成像方式和转化的非人类灵长类动物模型的基础上。我们研究了将人多能细胞区分为与肺部相关谱系（包括气道上皮细胞（AEC））的方法。具有独特的脚手架和物品的工程结构；并开发了有效标记，移植和监测恒河猴体内移植前体的命运的技术。 We are now poisoned to advance our prior discoveries and break new ground to address key questions related to iPSC-derived precursors to treat Congenital lung diseases, such as pulmonary survival deficiency, through the following Specific Aims: (1) Optimize lineage commitment of hiPSCs in 3D culture to enhance AEC differentiation and purity, and (2) Conduct proof-of-concept studies to evaluate fetal transplant efficiency and cell fate in vivo.我们将通过创新的成像范式（包括生物发光成像和阳性发射断层扫描/计算机断层摄影术（PET/ct））在3D培养中优化o键细胞种群，以增强谱系规范，并在体内评估移植效率和细胞命运。肺部维修能力有限，基于发展原理的再生概念，该原理是针对患者的年龄量身定制的，在转化私人模型中进行了测试，并且使用最先进的成像技术可能会对该领域产生重大影响。这些投资将提供新的见解，并指导转化研究的新途径，这些途径可能会对整个生命周期的儿童和所有年龄段产生重大影响和吸引人的好处。