A tissue engineered corneal epithelium replacement for animal testing using human stem cells

使用人类干细胞进行动物试验的组织工程角膜上皮替代物

基本信息

批准号：
BB/F019742/1
负责人：
Che Connon
金额：
$ 42.15万
依托单位：
University of Reading
依托单位国家：
英国
项目类别：
Research Grant
财政年份：
2008
资助国家：
英国
起止时间：
2008 至无数据
项目状态：
已结题

来源：
https://gtr.ukri.org/projects?ref=BB%2FF019742%2F1
关键词：
tissue engineered corneal epithelium replacement

项目摘要

The use of human stem cells in the treatment of serious disease or injury is currently undergoing a phase of rapid development. This intensive research has already produced new treatments for blindness. UK and Japanese scientists are now growing adult stem cells taken from donor corneas (the transparent tissue at the front of the eye) on specialised membranes to create new functional tissue. These regenerated tissues are then transplanted onto the surface of diseased or injured eyes leading to a restoration of the patients' sight. The use of human stem cells need not be limited to clinical theraputic use i.e. aimed at re-establishing vision in humans, they can aslo be used to significantly reduce the number of animals used in medical research. Presently, thousands of rabbits are needed every year to test for the toxic potential of new drugs and cosmetics. The method used in testing on rabbits eyes has changed little over 50 years. Now, by employing the scientific advancements recently made in therapeutic stem cell research to the manufacture of a human tissue based replica in culture, we aim to develop a human stem cell based non-animal alternative to drug and nanomaterial testing. The advantages of this are primarily that the effect of new chemicals/materials can be assessed without any animals being harmed and since the replica tissue is formed from human stem cells the results are also more representative. Furthermore, our non-animal model can assess water insoluble materials such as nanomaterials, something the animal models can not do well. To develop a human stem cell based non-animal alternative to drug testing we will essentially recreate the surface of the human eye in a plastic dish. Using adult stem cells isolated from adult corneal donor tissue and building upon the techniques sucessfully employed for corneal stem cell transplantation, we will identify a suitable protocol and substrate capable of both supporting the formation of a functional corneal epithelium in vitro and being easily sourced. The suitability of the newly developed human stem cell based non-animal alternative to drug testing will be established by vigorous testing of the model's response to known toxic and non-toxic agents. The model's response to toxicity testing will be robustly assessed by microscopy and established toxicity assays.

目前，人类干细胞在严重疾病或损伤的治疗中使用了快速发展的阶段。这项密集研究已经为失明产生了新的治疗方法。英国和日本科学家现在正在发展从供体角膜（眼前的透明组织）上的成年干细胞上，以创建新的功能组织。然后将这些再生组织移植到患病或受伤的眼睛表面，从而恢复患者的视力。人类干细胞的使用不必局限于临床治疗的使用，即旨在重新建立人类的视力，它们可以用来显着减少医学研究中使用的动物数量。目前，每年需要数千只兔子来测试新药和化妆品的有毒潜力。在兔子眼中测试的方法几乎没有变化超过50年。现在，通过采用最近在治疗性干细胞研究中做出的科学进步来制造基于人体组织的培养物，我们旨在开发一种基于人类干细胞的非动物替代药物和纳米材料测试的非动物替代品。它的优点主要是可以评估新化学物质/材料的影响而不会受到任何伤害，并且由于复制组织是由人干细胞形成的，因此结果也更具代表性。此外，我们的非动物模型可以评估不溶性材料，例如纳米材料，动物模型无法做到这一点。为了开发基于人类干细胞的非动物替代药物测试，我们将在塑料盘中基本上重现人眼表面。使用从成年角膜供体组织中分离出来的成年干细胞，并在成功用来用于角膜干细胞移植的技术上建立，我们将确定一种合适的方案和底物，能够既支持在体外支持功能性角膜上皮形成又可以轻松供应。通过对模型对已知有毒和无毒剂的反应进行剧烈测试，将建立新开发的基于人类干细胞的非动物替代药物替代品的适用性。该模型对毒性测试的反应将通过显微镜和确定的毒性测定进行牢固评估。