Collagen (I) homotrimer in age-related fibroses and tissue degeneration: evaluation as a stem cell biomarker

年龄相关纤维化和组织退化中的胶原 (I) 同源三聚体：作为干细胞生物标志物的评估

• 批准号: MR/J002909/1
• 负责人: Elizabeth Laird
• 金额: $ 44.35万
• 依托单位: University of Liverpool
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2012
• 资助国家: 英国
• 起止时间: 2012 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FJ002909%2F1
• 关键词: Collagen; homotrimer; age; related; fibroses

Collagen is the most abundant structural protein in the body. Collagen creates an environment within which cells reside and forms fibres that make tissues resilient to external stresses, for example during mechanical loading such as that occurs during normal locomotion. Collagen can be broken down and reformed by cells using biological enzymes; a normal process during growth and development. However, cancer cells invade tissues by degrading collagen whilst concurrently making their own non-degradable version of collagen, thereby creating a pathway for invasion. Non-degradable collagen has also been found in degenerative skeletal diseases such as osteoarthritis and osteoporosis as well as in fibrotic diseases including liver cirrhosis. The only other reports of non-degradable collagen are from embryonic cells or tissues, indicating that it might be produced by a type of stem cell and fulfil a normal biological function. Stem cells have the potential to form many different tissue types and their use has the potential to revolutionise approaches to regenerative medicine and tissue engineering. Embryonic stem cells can form all cell types in the body, but their use in research and in treatment trials is limited because of ethical considerations. Adult tissue stem cells are rare and may only be able to regenerate the tissue that they came from, but they could potentially be used to treat the patient from which they were isolated without subsequent immune rejection. The aim of this project is to determine whether non-degradable collagen is produced by embryonic and/or adult stem cells and to understand how cells control the genes responsible for this type of collagen production. This project will investigate how ageing affects the expression of these two forms of collagen and might predispose to disease. This research is important to characterise stem cells and to understand their role in the repair and regeneration of collagen-rich tissues. A clearer understanding of the role of particular types of collagen in ageing and disease would allow the development of biological markers for age- and disease-associated collagen. Such biological markers could be incorporated into tests to determine an individual's likelihood of developing diseases such as cancer, arthritis or osteoporosis. They could also be used to predict how quickly an individual might become frail and immobile in old age and to therefore tailor lifestyle recommendations (diet, exercise, built environment) and future anti-ageing medicines for particular groups. The results from this project would be informative for research programs that aim to use stem cells for transplantation or in tissue engineering.

胶原蛋白是体内最丰富的结构蛋白。胶原蛋白创造了一个环境，其中细胞驻留并形成纤维，使组织具有韧性，例如在机械载荷期间，例如在正常运动期间发生的纤维。胶原蛋白可以用生物学酶通过细胞分解并改革。在增长和发展过程中的正常过程。但是，癌细胞通过降解胶原蛋白而同时制作自己的不可降解的胶原蛋白，从而侵入组织，从而创造出侵袭途径。在退行性骨骼疾病中也发现了不可降解的胶原蛋白，例如骨关节炎和骨质疏松症以及包括肝肝硬化在内的纤维化疾病。唯一的不可降解胶原蛋白的报道来自胚胎细胞或组织，表明它可能是由一种干细胞产生的，并实现正常的生物学功能。干细胞有可能形成许多不同的组织类型，并且它们的使用有可能彻底改变再生医学和组织工程的方法。胚胎干细胞可以在体内形成所有细胞类型，但是由于伦理考虑，它们在研究和治疗试验中的使用受到限制。成年组织干细胞很少见，只能再生其来自的组织，但是它们有可能被用来治疗与之分离的患者，而无需随后的免疫排斥。该项目的目的是确定不可降解的胶原蛋白是否是由胚胎和/或成人干细胞产生的，并了解细胞如何控制负责这种类型的胶原蛋白产生的基因。该项目将研究衰老如何影响这两种形式的胶原蛋白的表达，并可能易于疾病。这项研究对于表征干细胞并了解其在富含胶原蛋白组织的修复和再生中的作用很重要。对特定类型的胶原蛋白在衰老和疾病中的作用的更清晰了解将允许开发与年龄和疾病相关的胶原蛋白的生物学标志物。可以将这种生物标记纳入测试中，以确定一个人患癌症，关节炎或骨质疏松症等疾病的可能性。它们还可以用来预测一个人在老年中可能会变得脆弱和不动的速度，从而为特定群体量身定制生活方式建议（饮食，运动，建筑环境）和未来的抗衰老药品。该项目的结果对于旨在使用干细胞进行移植或组织工程的研究计划是有益的。

项目成果

Identification and Characterization of Canine Ligament Progenitor Cells and Their Extracellular Matrix Niche

• DOI: 10.1021/acs.jproteome.8b00933
• 发表时间: 2019-03-01
• 期刊: JOURNAL OF PROTEOME RESEARCH
• 影响因子: 4.4
• 作者: Lee, Katie J.;Comerford, Eithne J.;Canty-Laird, Elizabeth G.
• 通讯作者: Canty-Laird, Elizabeth G.

54 The Stem Cell Niche In Tendon And Ligament - Investigating Alterations With Ageing And Disease

54 肌腱和韧带中的干细胞生态位 - 研究衰老和疾病引起的变化

• DOI: 10.1136/bjsports-2014-094114.54
• 发表时间: 2014
• 期刊: British Journal of Sports Medicine
• 影响因子: 18.4
• 作者: Lee K

Restricted differentiation potential of progenitor cell populations obtained from the equine superficial digital flexor tendon (SDFT).

• DOI: 10.1002/jor.22891
• 发表时间: 2015-06
• 期刊: Journal of orthopaedic research : official publication of the Orthopaedic Research Society
• 作者: Williamson KA;Lee KJ;Humphreys WJ;Comerford EJ;Clegg PD;Canty-Laird EG
• 通讯作者: Canty-Laird EG