CELLULAR ENGINEERING AND IMMUNOLOGICAL AGING

细胞工程和免疫老化

• 批准号: 3116281
• 负责人: ROBERT A GOOD
• 金额: $ 13.17万
• 依托单位: UNIVERSITY OF SOUTH FLORIDA
• 依托单位国家: 美国
• 财政年份: 1985
• 资助国家: 美国
• 起止时间: 1985-01-01 至 1987-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3116281
• 关键词: B lymphocyte; T lymphocyte; aging; antibody formation; autoimmune disorder; bone marrow transplantation; cellular pathology; genetic manipulation; graft versus host disease; human subject; immune complex; immunogenetics; immunoregulation; leukocyte activation /transformation; major histocompatibility complex; radiation genetics; tissue /cell culture; tissue mosaicism

Short-lived autoimmune-prone mice which develop relatively early in life all of the diseases of aging, e.g., amyloidosis, autoimmunities, vascular diseases, coronary disease, immunodeficiency which renders them susceptible to infection, hyalinizing renal disease associated with high levels of circulating immunocomplexes and immunocomplex injuries, and a high frequency of malignancy, have a genetic fault that may be correctable by cellular engineering. We propose that the life span short-lived autoimmune-prone mice might be greatly prolonged and development of diseases of aging prevented if we can transplant marrow to these short-lived autoimmune-prone mice relatively early in life without producing graft-versus-host reaction (GVHR). This feat would require transplanting marrow to introduce genetically distinct stem cells. The stem cells should come from a strain of mice genetically programmed for long life, and late immunologic disorganization. Such a donor should be resistant to development of autoimmunity, and the marrow transplant should not produce GVHR.

短暂的自身免疫性易受免疫性小鼠，生命早期发展 衰老的所有疾病，例如淀粉样变性，自身免疫，血管 疾病，冠状动脉疾病，免疫缺陷使它们易感 要感染，与高水平有关的透明肾脏疾病 循环免疫复合物和免疫复合损伤，高 恶性肿瘤的频率，具有遗传缺陷，可能可以通过 蜂窝工程。 我们建议寿命短暂 自身免疫性容易发生的老鼠可能会大大延长 如果我们可以将骨髓移植到这些疾病 短暂寿命的自身免疫性易免疫的老鼠相对较早而没有 产生移植物与宿主反应（GVHR）。 这项壮举需要 移植骨髓以引入遗传上不同的干细胞。 这 干细胞应来自用于基因编程的小鼠菌株 长寿和晚期免疫混乱。 这样的捐助者应该是 对自身免疫的发展和并且从骨髓移植的能力应 不产生GVHR。