Paradigms of Wound Healing and Fibrosis in the Eye

目前，参与伤口愈合和纤维化的间充质细胞的前体的身份还不清楚。 辩论我们提出了一个新的范例，其中这些细胞来自一个独特的修复亚群 与上皮组织细胞正常共存的祖细胞。我们已经证明了这些 修复透镜和角膜中的细胞。在透镜中，这些修复祖细胞通过以下方式对损伤迅速作出反应： 通过一种独立于DNA复制的机制扩大种群规模，但可能与它们的 不寻常的多倍性特征。介导祖细胞扩增的信号， 将修复细胞重编程为修复表型并将修复细胞快速靶向至伤口边缘， 未知虽然修复细胞在损伤部位作为愈合过程的调节剂发挥作用，但它们也 具有转分化为肌成纤维细胞表型的潜力，该细胞类型与纤维化有关。这 一项提案在透镜和角膜损伤模型中检查了这种新的伤口愈合范例， 问题：1）修复祖细胞是造血谱系的新后代吗？2)是什么 修复细胞祖细胞响应宿主上皮损伤而迅速扩增的机制？第三章 间充质祖细胞是如何向伤口边缘迁移的？4)什么是命运的 间充质细胞在完成调节伤口修复的工作后？;（5）条件是什么 其诱导修复细胞获得与疾病状态相关的成熟肌成纤维细胞表型， 纤维化吗这些研究有望在细胞生物学和伤口愈合领域产生重大影响 通过将伤口愈合调节因子和肌成纤维细胞来源的研究转移到这种新的祖细胞上， 人口

Currently the identity of precursors of the mesenchymal cells involved in wound healing and fibrosis are under debate. We propose a novel paradigm in which these cells descend from a unique subpopulation of repair progenitor cells that coexist normally with the cells of epithelial tissues. We have shown the presence of these repair cells in the lens and cornea. In the lens these repair progenitor cells rapidly respond to injury by expanding their population size through a mechanism independent of DNA replication, but likely related to their unusual characteristic of polyploidy. The signals that mediate the expansion of the progenitor cells, their reprogramming to a repair phenotype and the rapid targeting of the repair cells to the wound edge are unknown. While the repair cells function at the site of injury as regulators of the healing process, they also have the potential to trandifferentiate to a myofibroblast phenotype, the cell type linked to fibrosis. This proposal examines this novel wound healing paradigm in both lens and cornea injury models with the following questions: 1) Are the repair progenitor cells novel descendents of a hematopoietic lineage?; 2) What is the mechanism by which repair cell progenitors rapidly expand in response to injury of their host epithelium?; 3) How are mesenchymal progenitor cells signaled to migrate to the wound edge?; 4) What is the fate of the mesenchymal cells after they complete their job of regulating wound repair?; and 5) What are the conditions that induce the repair cells to acquire the mature myofibroblast phenotype associated with disease states such as fibrosis? These studies are expected to have a major impact in the fields of cell biology and wound healing by shifting the study of the regulators of wound healing and source of myofibroblasts to this novel progenitor population.