Pneumografting - a novel cell-based therapy for emphysema

肺移植——一种新型的基于细胞的肺气肿疗法

基本信息

批准号：
7334362
负责人：
EDWARD P INGENITO
金额：
$ 58.37万
依托单位：
BRIGHAM AND WOMEN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2007
资助国家：
美国
起止时间：
2007-09-28 至 2011-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7334362
关键词：
Affect Air Alveolar Area Autologous Back Biology Biopsy Blood Vessels Cell Count Cell Therapy Cells Cellularity Clinical Trials Collagen Complex Condition Cultured Cells Data Development Devices Disease Elastic Fiber Elements Epithelial Cell Proliferation Experimental Models Extracellular Matrix Family Fiber Fibroblast Growth Factor Genes Goals Grant Growth Growth Factor Harvest Healed Homeostasis Human Injury Intervention Investigation Investigational New Drug Application Localized Lung Lung Volume Reductions Maintenance Mechanics Mesenchymal Methodology Methods Natural regeneration Numbers Perfusion Pharmaceutical Preparations Phase Physicians Physiological Pilot Projects Polymers Process Property Protein Tyrosine Kinase Pulmonary Emphysema Reaction Reagent Research Personnel Scaffolding Protein Signal Transduction Site Solutions Stem cells Stimulus Stress Stretching Structure of parenchyma of lung Techniques Testing Therapeutic Thinking Time Tissue Harvesting Tissues Trypsin Week base biocompatible polymer cell type conditioning healing member novel pressure prevent programs response scaffold tissue regeneration transcription factor transmission process

项目摘要

DESCRIPTION (provided by applicant): Recent studies suggest that reparative cells which contribute to healing in the lung following injury also possess regenerative capacity. Although the biology of post-natal lung regeneration is not well understood, mechanical pre-stress appears to be an absolute requirement for tissue regeneration to occur. Emphysema, a disease characterized by tissue destruction, is a potential target for cell-based therapy. This disease is associated with: 1) loss of resident reparative cells; 2) loss of the extracellular matrix that transmits pre-stress signaling; 3) and loss of pre-stress itself, the very signal required to trigger regenerative responses. Although these factors represent obstacles to the development of regenerative therapeutic strategies for emphysema, preliminary studies in our lab show that modulation of mesenchymal and epithelial cell proliferation using members of the fibroblast growth factor family complexed to carrier molecules in a biocompatible polymer can promote expansion of parenchymal tissues. The polymer scaffold, an air containing foam with mechanical properties similar to healthy lung tissue, effectively transmits stress to reparative/progenitor cells to promote proliferation and remodeling. Studies proposed here will test the hypothesis that 1) therapeutic post-natal lung tissue growth in emphysema can be achieved by augmenting the lung's innate healing response using growth factors to direct endogenous reparative lung cells following a localized mild injury; and that 2) the magnitude of this response can be modulated by altering pre-stress using concomitant bronchoscopic lung volume reduction therapy to increase transpulmonary pressures. We intend to advance this approach, known as pneumografting, into human trials under a physician-sponsored Investigation New Drug Application.

描述（由申请人提供）：最近的研究表明，在受伤后有助于肺部愈合的修复细胞也具有再生能力。尽管尚不清楚产后肺部再生的生物学，但机械前压力似乎是组织再生的绝对要求。肺气肿是以组织破坏为特征的疾病，是基于细胞治疗的潜在靶标。该疾病与以下疾病有关：1）居民修复细胞的丧失； 2）损失传递预压力信号传导的细胞外基质； 3）和损失预压力本身，触发再生反应所需的信号。尽管这些因素代表了肺气肿再生治疗策略发展的障碍，但在我们的实验室中，初步研究表明，使用成纤维细胞生长因子的成员对生物相容性聚合物中载体分子的成员进行了调节的间质和上皮细胞增殖的调节可以促进羊皮组织组织的扩张。聚合物支架是一种含有与健康肺组织相似的机械性能的泡沫的空气，有效地将应力传递到修复/祖细胞中，以促进增殖和重塑。这里提出的研究将检验以下假设，即1）可以通过使用生长因子来直接导致内源性调节性肺细胞在局部轻度损伤后加强肺的先天愈合反应来实现肺气肿的肺部肺组织生长； 2）可以通过使用伴随的支气管镜肺体积减少疗法来改变预压来调节这种反应的大小，从而增加肺压力。我们打算根据医师赞助的调查新药应用将这种称为肺炎的方法（称为肺炎）提高到人类试验。