Stem-Cell Properties of Human Corneal Keratocytes

人角膜角膜细胞的干细胞特性

• 批准号: 8461204
• 负责人: Jennifer Rayming Chao
• 金额: $ 21.39万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2015-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8461204
• 关键词: Address; Affect; Allogenic; Biological Assay; Blindness; Bullous Keratopathy; Cell Culture Techniques; Cell Lineage; Cells; Chick Embryo; Cicatrix; Cornea; Corneal Diseases; Corneal Endothelium; Country; Data; Disease; Embryo; Endothelial Cells; Environment; Fuchs' Endothelial Dystrophy; Functional disorder; Goals; Healthcare; Human; Individual; Instruction; K-Series Research Career Programs; Keratoconus; Keratoplasty; Laboratories; Life; Mentorship; Neural Crest; Operative Surgical Procedures; Patients; Penetrating Keratoplasty; Property; Quail; Regenerative Medicine; Reporting; Research; Research Personnel; Resources; Signal Transduction; Stem cells; Stromal Cells; Structure; System; Tissues; Trachoma; Transplantation; United States; Vision; Work; age effect; base; career; corneal scar; experience; human embryonic stem cell; in vivo; interest; meetings; operation; postnatal; postnatal human; progenitor; self-renewal; stem cell biology

My objectives in seeking a KGB career development award are two-fold: 1) to examine the multipotentiality of post-natal human keratocytes and human neural crest stem cells in ovo and; 2) to develop my career as an independent investigator in stem cell biology by hands-on research experience, didactics and mentorship. The most common causes of human corneal blindness are visually significant stromal scarring and endothelial cell dysfunction. In the US, it is predicted that with the advent of refractive surgery, the supply of donor corneas suitable for transplantation will be significantly reduced. Because of these challenges, there is significant interest in pursuing the use of cells that have the ability to self-renew, differentiate into multiple cell lineages, and remodel tissues in vivo, in the treatment of corneal disorders. While there have been recent reports of human cornea stem cells that can be induced to express markers consistent with multi- potency in cell culture, little is known about the multi-potentiality of differentiated cornea stromal cells. Our preliminary data indicate that human keratocytes isolated from postnatal corneas have the ability to differentiate into neural crest derivatives in the chick embryonic environment. This is the first evidence, albeit early, that human keratocytes and postnatal (versus embryonic) keratocytes retain the multi-potentiality of the neural crest precursors from which they are derived as partially restricted progenitors. The working hypothesis of this proposal is that human postnatal keratocytes retain the multi-potency of their neural crest precursors and have the ability to differentiate into neural crest derivatives, including other ocular tissues. Further, the chick embryonic microenvironment likely contains the adequate signals required to differentiate human neural crest stem cells into ocular tissues, as well as other neural crest-derived structures. Three specific aims will be addressed; Aim 1; characterize the multipotentiality of human post-natal keratocytes, using the chick embryonic environment as an assay system. Aim 2: examine the effects of age and differentiation status on the multipotentiality of human keratocytes. Aim 3; explore the potential for human neural crest stem cells to form neural crest ocular derivatives in ovo. RELEVANCE (See instructions); The availability of donor corneas often limits the ability to treat corneal scarring, the second most common cause of blindness worldwide. Our goal is to understand the ability of post-natal human keratocytes and neural crest stem cells to differentiate into ocular tissues in an embryonic environment. This will serve as a basis for determining the feasibility of creating specialized cells for use in regenerative medicine.

我寻求克格勃职业发展奖的目标有两个：1）考察 卵内产后人角膜细胞和人神经嵴干细胞； 2）发展我的职业生涯 通过实践研究经验、教学和指导成为干细胞生物学的独立研究者。 人类角膜失明的最常见原因是视觉上明显的基质疤痕和 内皮细胞功能障碍。在美国，预计随着屈光手术的出现， 适合移植的供体角膜将会明显减少。由于这些挑战， 对使用具有自我更新、分化成多种能力的细胞非常感兴趣 细胞谱系，并在体内重塑组织，用于治疗角膜疾病。虽然已经有 最近有报道称，人类角膜干细胞可以被诱导表达与多因素一致的标记物。 尽管细胞培养中的潜能，但人们对分化的角膜基质细胞的多潜能知之甚少。我们的 初步数据表明，从出生后角膜中分离出的人类角膜细胞能够 在鸡胚胎环境中分化为神经嵴衍生物。这是第一个证据，尽管 早期，人类角膜细胞和出生后（相对于胚胎）角膜细胞保留了多种潜能 神经嵴前体，它们作为部分限制性祖细胞衍生。工作中 该提议的假设是人类出生后角膜细胞保留其神经嵴的多功能性 前体并具有分化成神经嵴衍生物的能力，包括其他眼组织。 此外，鸡胚胎微环境可能包含分化所需的足够信号 人类神经嵴干细胞进入眼组织以及其他神经嵴衍生结构。三 将解决具体目标；目标1；表征人类出生后角膜细胞的多潜能性， 使用鸡胚胎环境作为测定系统。目标 2：检查年龄的影响 人角膜细胞多能性的分化状态。目标3；探索人类的潜力 神经嵴干细胞在卵内形成神经嵴眼部衍生物。 相关性（参见说明）； 供体角膜的可用性通常限制了治疗角膜疤痕的能力，角膜疤痕是第二常见的问题 导致全世界失明的原因。我们的目标是了解出生后人类角膜细胞的能力和 神经嵴干细胞在胚胎环境中分化成眼组织。这将作为 确定创建用于再生医学的特殊细胞的可行性的基础。