Stem Cells for Corneal Engineering

角膜工程干细胞

• 批准号: 7613878
• 负责人: JAMES L FUNDERBURGH
• 金额: $ 8.23万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-15 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7613878
• 关键词: Address; Adult; Aging; Architecture; Biological; Biological Markers; Biomedical Engineering; Biophysics; Bioprosthesis device; Blindness; Cell Therapy; Cells; Characteristics; Cicatrix; Collagen; Collagen Fibril; Condition; Connective Tissue; Cornea; Corneal Injury; Corneal Stroma; Deposition; Engineering; Epithelial; Exhibits; Extracellular Matrix; Fibroblasts; Generations; Goals; Healed; Human; Implant; In Vitro; Individual; Injection of therapeutic agent; Knockout Mice; Laboratories; Lamellar Keratoplasty; Left; Location; Molecular; Mus; Myofibroblast; Natural regeneration; Neural Crest; Operative Surgical Procedures; Pathologic; Pathology; Phenotype; Population; Property; Proteoglycan; Protocols documentation; Public Health; Research Personnel; Role; Serial Passage; Stem cells; Stress; Structure; Technology; Testing; Therapeutic Intervention; Time; Tissues; Transforming Growth Factor beta; Transplantation; Vision; adult stem cell; base; cell water; corneal scar; falls; healing; human stem cells; in vivo; limbal; lumican; mouse model; novel; programs; remediation; repaired; research study; response; scaffold; transdifferentiation

Aging of the population and popularity of refractive surgery threaten adequacy of the cornea supply used for transplantation in the USA. World-wide, cornea donations already fall short, leaving 6-8 million individuals suffering corneal blindness. Engineered corneas, grown in the laboratory and available on demand, will ultimately help alleviate this public health problem. The long-term goal of this project is to develop corneal equivalents for transplantation using cultured human stem cells. Initially the project will focus on the corneal stroma, the connective tissue that makes up 90% of the corneal mass. We have recently discovered a population of cells from human corneal stroma with properties of adult stem cells. Unlike keratocytes, the human corneal stromal stem cells (hCSSC) can be passaged numerous times in culture but still retain the ability to become keratocytes in vivo and in vitro. We hypothesize that the human corneal stromal stem cells participate in response to corneal injury and can regenerate transparent stromal tissue both in vivo and in vitro.. This hypothesis will be tested (1) by demonstrating the influx of hCSSC into pathological human corneas and by documenting the fate of hCSSC introduced into normal and healing mouse corneas in vivo. (2) Lumican null mice which develop opacity similar to corneal scars and corneas scarred by injection of transforming growth factor beta will be treated with hCSSC to investigate observed ability of these cells to restore corneal transparency. (3) Tissue equivalents produced in vitro by hCSSC will be implanted into mouse cornea to investigate the molecular and structural requirements for transparency in stromal tissue. Successful accomplishment of these aims will elucidate biological roles of the newly discovered adult stromal stem cells and provide novel information about how the stromal ultrastructure and corneal transparency are maintained in vivo. The experiments will also develop essential technologies for cell-based therapy for corneal scars and for fabrication of bioengineered tissue which could be used directly for lamellar keratoplasty or serve as the basis of a fully bioengineered cornea.

人口老龄化和屈光手术的普及威胁着用于手术的角膜供应的充足性 移植到美国。在世界范围内，角膜捐赠已经不足，只剩下 6-800 万人 患有角膜失明。在实验室培育并按需提供的工程角膜将 最终有助于缓解这一公共卫生问题。该项目的长期目标是开发角膜 使用培养的人类干细胞进行移植的等效物。最初该项目将重点关注角膜 基质，即构成角膜质量 90% 的结缔组织。我们最近发现了一个 来自人类角膜基质的细胞群，具有成体干细胞的特性。与角膜细胞不同， 人角膜基质干细胞（hCSSC）可以在培养物中传代多次，但仍保留 在体内和体外成为角膜细胞的能力。我们假设人角膜基质干细胞 参与对角膜损伤的反应，并且可以在体内和体内再生透明基质组织 体外.. 该假设将通过证明 hCSSC 流入病理人类中进行检验 (1) 角膜并记录了 hCSSC 引入正常和愈合小鼠角膜体内的命运。 (2) Lumican 缺失小鼠出现类似于角膜疤痕的混浊，并且通过注射 转化生长因子β将用hCSSC处理，以研究观察到的这些细胞的能力 恢复角膜透明度。 (3) hCSSC体外产生的组织等效物将被植入 小鼠角膜研究基质组织透明度的分子和结构要求。 这些目标的成功实现将阐明新发现的成体基质的生物学作用 干细胞并提供有关基质超微结构和角膜透明度如何的新信息 维持在体内。这些实验还将开发基于细胞的治疗的基本技术 角膜疤痕和用于制造可直接用于层状角膜的生物工程组织 角膜移植术或作为完全生物工程角膜的基础。