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是两方面：1） 产后人角膜细胞和人类神经rest干细胞，以及； 2）发展我的职业 通过动手研究经验，教学和指导，干细胞生物学领域的独立研究者。 人角膜失明的最常见原因是视觉上重要的基质疤痕， 内皮细胞功能障碍。在美国，可以预测，随着屈光手术的出现 适合移植的供体角膜将大大减少。由于这些挑战， 对于追求具有自我更新，分为多重能力的细胞的使用非常有兴趣 细胞谱系和体内重塑组织，以治疗角膜疾病。虽然有 最新的人角膜干细胞的报道可引起表达与多数相一致的标记 细胞培养的效力，对分化角膜基质细胞的多电位性知之甚少。我们的 初步数据表明，从产后角膜分离的人角膜细胞具有能力 分化为雏鸡胚胎环境中的神经rest衍生物。这是第一个证据，尽管 早期，人类角膜细胞和产后（与胚胎）角膜细胞保留了多势性 它们作为部分限制的祖细胞的神经rest前体。工作 该提议的假设是人类后产后角膜细胞保留了其神经rest的多功能 前体并具有分化为神经rest衍生物（包括其他眼组织）的能力。 此外，雏鸡胚胎微环境可能包含分化所需的足够信号 人神经rest干细胞进入眼组织，以及其他神经rest衍生的结构。三 将解决具体目标；目标1;表征人类产后角膜细胞的多能性， 使用雏鸡胚胎环境作为测定系统。目标2：检查年龄的影响和 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rest干细胞在OVO中形成神经rest的眼部衍生物。 相关性（请参阅说明）； 供体角膜的可用性通常会限制治疗角膜疤痕的能力，第二个最常见的能力 全球失明的原因。我们的目标是了解产后人类角膜细胞的能力和 神经rest干细胞在胚胎环境中分化为眼组织。这将成为 确定创建专业细胞用于再生医学的可行性的基础。