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角膜移植的角膜供应的充足性。 移植在美国。在世界范围内，角膜捐赠已经不足，剩下600 - 800万人 患有角膜失明在实验室中培养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 用于使用培养的人类干细胞进行移植的等同物。最初，该项目将集中在角膜 基质，即构成角膜质量90%的结缔组织。我们最近发现了一个 来自人角膜基质的具有成体干细胞特性的细胞群。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，但仍然保留了角膜基质干细胞（hCSSC）。 在体内和体外成为角膜细胞的能力。我们假设人类角膜基质干细胞 参与对角膜损伤的反应，并且可以在体内和体外再生透明基质组织。 体外..该假设将通过证实hCSSC流入病理性人类淋巴细胞来检验（1）。 角膜中，并通过记录体内引入正常和愈合小鼠角膜中的hCSSC的命运。 (2)Lumican敲除小鼠，其产生类似于角膜瘢痕的不透明和通过注射 将用hCSSC处理转化生长因子β，以研究观察到的这些细胞 恢复角膜透明度。(3)由hCSSC体外产生的组织等同物将被植入 小鼠角膜，以研究基质组织中透明性的分子和结构要求。 这些目标的成功实现将阐明新发现的成体间质细胞的生物学作用。 并提供了关于基质超微结构和角膜透明度如何 保持在体内。这些实验还将为基于细胞的治疗开发必要的技术， 角膜瘢痕和用于制造可直接用于板层的生物工程组织 角膜移植术或作为完全生物工程角膜的基础。