Matrix remodeling in microfluidic co-culture
微流控共培养中的基质重塑
基本信息
- 批准号:9087443
- 负责人:
- 金额:$ 20.92万
- 依托单位:
- 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:2016-04-11 至 2018-03-31
- 项目状态:已结题
- 来源:
- 关键词:AsthmaAttentionBiological ModelsBiomedical EngineeringBlood capillariesCell CommunicationCell CountCell Culture TechniquesCellsChronicChronic Obstructive Airway DiseaseCoculture TechniquesCuesDevelopmentDiseaseEndotheliumEpitheliumExtracellular MatrixFibroblastsFibrosisGelGoalsHealthHomeostasisHumanImageImage AnalysisIndividualInjuryInvestigationLiquid substanceLungLung diseasesMaintenanceMediator of activation proteinMicrofluidicsNatureNoiseParacrine CommunicationPathogenesisPathologicPerfusionPhysiologicalProcessProteomicsPulmonary FibrosisPulmonary HypertensionResourcesSamplingSideSignal TransductionSystemTherapeuticTimeTissuesTransforming Growth Factor betacapillarycell typedesigndifferential expressionin vivomeetingsnovelpersonalized medicinepreventpublic health relevanceresearch studystemtherapeutic evaluation
项目摘要
DESCRIPTION (provided by applicant): Remodeling of the extracellular matrix (ECM) is central to the pathogenesis of chronic respiratory diseases, including pulmonary fibrosis, pulmonary hypertension, asthma and COPD. While much emphasis has been placed on studying individual cell types and how they interact with the ECM, comparatively little attention has focused on how homeostatic maintenance of the ECM is coordinated amongst multiple lung resident cell types, and how cell interactions in the setting of injury or disease either restore homeostasis or generate pathological matrix remodeling. A major limitation preventing investigation of these crucial cell-cell and cell-matrix interactions is the absence of experimentally tractable multicellular culture systems which incorporate 3D matrices capable of long-term remodeling. Another major limitation stems from the limited number, availability, proliferative capacity, and phenotypic stability of primary human cells, which are a critical resource if we are to elucidate the "normal" homeostatic and "pathological" matrix remodeling processes that underlie human health and disease. Our goal in this proposal is to develop a cell culture model system that (1) facilitates long-term culture study of homeostatic and pathologic matrix remodeling under the control of multiple interacting primary lung cell types; (2) enables repeated non-destructive imaging and sampling to identify cellular and soluble cues that correlate with, and ultimately predict, the cell-cell and cell-matrix interactions underlying matri remodeling; and (3) provides a platform for studying primary human cells in small quantities as a step toward enhanced phenotypic fidelity and personalized medicine. These design goals will be met through two interrelated specific aims. In Aim 1 we will develop and optimize a microfluidic system and culture conditions permitting stable, long-term co-culture of lung epi/endothelium and extracellular matrix-embedded fibroblasts. We will evaluate multiple physiologic metrics of ECM and tissue remodeling in co-culture, and evaluate their sensitivity and signal to noise ratio using culture conditions known to promote matrix/tissue remodeling in vivo (e.g. TGF-beta stimulation). In Aim 2 we will incorporate primary human cells into the microfluidic co-culture system as a step toward personalized medicine, therapeutic prioritization, and biologic discovery. We will use approved and failed anti-fibrosis therapies to assess the predictive capacity of this system as proof of concept. To capitalize on the discovery capabilities of the system, we will collect matrix compartment fluid samples for proteomic analysis to identify novel candidate mediators differentially expressed during matrix remodeling. This project will generate a new experimental platform that enables repeated real-time analysis of cell-cell and cell-matrix interactions during matrix remodeling, a process central to the pathogenesis of multiple respiratory diseases. Incorporation of primary human cells with low or no passaging into the platform will enhance the biofidelity of experiments and offer a unique resource for personalized medicine, therapeutic evaluation and biologic discovery in the realm of lung matrix remodeling.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Daniel J. Tschumperlin其他文献
788 – Microrna Let-7F is Overexpressed in Colonic Smooth Muscle from Patients with Slow Transit Constipation, Reduces Voltage-Gated Sodium Channel Na<sub>v</sub>1.5 Current Density and Gastrointestinal Smooth Muscle Contractility
- DOI:
10.1016/s0016-5085(19)37205-1 - 发表时间:
2019-05-01 - 期刊:
- 影响因子:
- 作者:
Amelia Mazzone;Peter R. Strege;Constanza Alcaino;Andrew J. Haak;Daniel J. Tschumperlin;Mona El Refaey;Peter J. Mohler;Yujiro Hayashi;Tamas Ordog;Stefan S. Calder;Peng Du;Simon J. Gibbons;Gianrico Farrugia;Arthur Beyder - 通讯作者:
Arthur Beyder
EVALUATION OF THE IN VIVO EFFICACY OF THE JAK INHIBITOR AZD1480 AGAINST UTERINE LEIOMYOMAS IN A PATIENT-DERIVED XENOGRAFT MOUSE MODEL
- DOI:
10.1016/j.fertnstert.2023.05.015 - 发表时间:
2023-07-01 - 期刊:
- 影响因子:
- 作者:
Michael F. Neblett;Merrick T. Ducharme;Jeffrey A. Meridew;Andrew J. Haak;Daniel J. Tschumperlin;Elizabeth A. Stewart - 通讯作者:
Elizabeth A. Stewart
SOCS domain targets ECM assembly in lung fibroblasts and experimental lung fibrosis
SOCS 结构域靶向肺成纤维细胞和实验性肺纤维化中的细胞外基质组装
- DOI:
10.1038/s41598-024-83187-9 - 发表时间:
2024-12-30 - 期刊:
- 影响因子:3.900
- 作者:
Carina Magdaleno;Daniel J. Tschumperlin;Narendiran Rajasekaran;Archana Varadaraj - 通讯作者:
Archana Varadaraj
Daniel J. Tschumperlin的其他文献
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{{ truncateString('Daniel J. Tschumperlin', 18)}}的其他基金
Fibrogenic activation and memory in the lung mesenchyme
肺间质的纤维化激活和记忆
- 批准号:
10558822 - 财政年份:2022
- 资助金额:
$ 20.92万 - 项目类别:
2021 Lung Development, Injury and Repair Gordon Research Conference and Gordon Research Seminar
2021年肺发育、损伤与修复戈登研究会议暨戈登研究研讨会
- 批准号:
10217714 - 财政年份:2021
- 资助金额:
$ 20.92万 - 项目类别:
Therapeutic ECM Resorption in Cellular Systems and Precision Cut Lung Slices.
细胞系统中的治疗性 ECM 吸收和精密切割肺切片。
- 批准号:
10530660 - 财政年份:2020
- 资助金额:
$ 20.92万 - 项目类别:
Therapeutic ECM Resorption in Cellular Systems and Precision Cut Lung Slices.
细胞系统中的治疗性 ECM 吸收和精密切割肺切片。
- 批准号:
10318078 - 财政年份:2020
- 资助金额:
$ 20.92万 - 项目类别:
Therapeutic ECM Resorption in Cellular Systems and Precision Cut Lung Slices.
细胞系统中的治疗性 ECM 吸收和精密切割肺切片。
- 批准号:
10025548 - 财政年份:2020
- 资助金额:
$ 20.92万 - 项目类别:
Screening Fibroblast-Matrix Stiffness Interactions to ID New Fibrosis Therapies
筛选成纤维细胞-基质硬度相互作用以识别新的纤维化疗法
- 批准号:
8445051 - 财政年份:2013
- 资助金额:
$ 20.92万 - 项目类别:
Screening Fibroblast-Matrix Stiffness Interactions to ID New Fibrosis Therapies
筛选成纤维细胞-基质硬度相互作用以识别新的纤维化疗法
- 批准号:
8712545 - 财政年份:2013
- 资助金额:
$ 20.92万 - 项目类别:
Epithelial-Mesenchymal Interactions in Fibrosis Resolution
纤维化消退中的上皮-间质相互作用
- 批准号:
10655172 - 财政年份:2009
- 资助金额:
$ 20.92万 - 项目类别:
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