Pneumografting - a novel cell-based therapy for emphysema

描述（由申请人提供）： 最近的研究表明，有助于肺损伤后愈合的修复细胞也具有再生能力。虽然出生后肺再生的生物学还没有很好的理解，机械预应力似乎是组织再生发生的绝对要求。肺气肿是一种以组织破坏为特征的疾病，是基于细胞的治疗的潜在靶点。这种疾病与以下因素有关：1）常驻修复细胞的损失; 2）传递预应激信号的细胞外基质的损失; 3）以及预应激本身的损失，这是触发再生反应所需的信号。虽然这些因素代表了肺气肿再生治疗策略发展的障碍，但我们实验室的初步研究表明，使用与生物相容性聚合物中的载体分子复合的成纤维细胞生长因子家族成员调节间充质和上皮细胞增殖可以促进实质组织的扩张。聚合物支架是一种含有空气的泡沫，具有与健康肺组织相似的机械性能，有效地将应力传递给修复/祖细胞，以促进增殖和重塑。本文提出的研究将检验以下假设：1）肺气肿的治疗性出生后肺组织生长可通过使用生长因子增强肺的先天愈合反应来实现，以在局部轻度损伤后指导内源性修复性肺细胞; 2）该反应的大小可通过使用伴随的支气管镜肺减容治疗改变预压力来调节，以增加经肺动脉压。我们打算将这种称为肺移植的方法推进到由医生赞助的新药研究申请的人体试验中。

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.