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3D Bioprinted lung cancer models for drug screening

用于药物筛选的 3D 生物打印肺癌模型

基本信息

批准号：
10907367
负责人：
Marc Ferrer
金额：
$ 226.91万
依托单位：
NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10907367
关键词：
3-Dimensional Aftercare Air Animal Model Antineoplastic Agents Biological Assay Bladder Breast Cancer Cell Growth Cancer Detection Cancer Model Cell Line Cell model Collection Development Drug Modelings Drug Screening Endothelial Cells Epithelial Cells Epithelium Fibroblasts Fluorescence Functional disorder Genetically Engineered Mouse Goals Growth Human Immunodeficient Mouse In Vitro Label Liquid substance Lung Malignant Neoplasms Malignant neoplasm of lung Malignant neoplasm of urinary bladder Mesothelial Cell Mesothelioma Modeling Monitor Morphology National Center for Advancing Translational Sciences Neoplasm Metastasis Non-Small-Cell Lung Carcinoma Oncology Patients Pericytes Physiological Physiology Pleura Pleural Preclinical Testing Proteins Protocols documentation Recurrent disease Structure of parenchyma of lung Surface Therapeutic Therapeutic Intervention Tissue Model Tissues Toxicity Tests Vascularization Work Xenograft procedure airway epithelium angiogenesis biomarker discovery bioprinting cancer cell cellular imaging clinical efficacy drug development drug discovery efficacy testing lentivirally transduced lung basal segment monolayer neoplastic cell new therapeutic target novel therapeutics predictive test prevent screening transcriptomics tumor tumor growth vasculogenesis

项目摘要

We have established protocols for the bioprinting of a lung vascularized basal tissue using primary lung endothelial cells, pericytes and fibroblasts. IHC and fluorescence microcopy was used to establish vasculogenesis and angiogenesis. We also developed protocols for the labeling of cancer cells with lentivirus transduced florescence proteins and monitor tumor formation in the tissue for a set of bladder cancer cells with different metastatic origin. We are also establishing a model of the lung pleural by layering primary mesothelial cells on top of the vascularized lung base tissue to create model of mesothelioma in a pleura tissue. Finally, we have also established protocols to layer and differentiate small airway epithelial cells (SAEC) at the air-liquid interface (ALI) and have added fluorescently labeled NSCLC tumor cells and demonstrated formation of tumors on the lung epithelial ALI tissue. Currently, we are exploring the growth of NSCLC cancer cells in the the whole vascularized lung tissue with a differentiated SAEC layer at the ALI. Once this work is completed, we will implement the HTS of the NCATS oncology collection looking for compounds that prevent NSCLC tumor growth in a lung tissue model.

我们已经建立了使用原代肺内皮细胞、周细胞和成纤维细胞进行肺血管化基底组织生物打印的方案。采用免疫组化和荧光显微复制法建立血管新生和血管新生。我们还开发了用慢病毒转导的荧光蛋白标记癌细胞的方案，并监测组织中具有不同转移来源的一组膀胱癌细胞的肿瘤形成。我们还建立了一个肺胸膜模型，通过将原发性间皮瘤细胞分层在血管化的肺基底组织上，以创建胸膜组织中的间皮瘤模型。最后，我们还建立了在气液界面（ALI）分层和分化小气道上皮细胞（SAEC）的方案，并添加了荧光标记的NSCLC肿瘤细胞，并证实了肺上皮ALI组织上肿瘤的形成。目前，我们正在探索非小细胞肺癌细胞在ALI处具有分化SAEC层的全血管化肺组织中的生长。一旦这项工作完成，我们将实施NCATS肿瘤学收集的HTS，在肺组织模型中寻找阻止非小细胞肺癌肿瘤生长的化合物。