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Establishment of the system to study the function and therapy of deseases in human organs maintained in SCID mice

SCID小鼠人体器官功能及疾病治疗研究体系的建立

基本信息

批准号：
07558078
负责人：
NOMURA Taisei
金额：
$ 8万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1997
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07558078/
关键词：
Human tissue in mice Improved SCID mice Morphology and function Human Deseases Therapeutic model Thyroid function Human skin Solar sensitivity

项目摘要

We established an experimental system to investigate the development, morphology, physiology and disorder of human organ and tissue which are maintained in the severe combined immunodeficient mice (SCID) for long period.1. Long maintenance of normal human tissues and examination of the function.Normal human organs and tissues (bone marrow, skin, thyroid, colon, stomach, liver, lung, fetal tissues, etc.) were maintained for 2-3 years in the improved SCID mice. These human organs showed normal morphology and function. In particular, thyroid function remained active by the treatment with thyroid stimulating hormone (TSH). Labeled iodine was incorporated into human thyroid gland maintained in the SCID mice more actively by the injection of human TSH to the mice. Human embryonic tissues also well developed and grew rapidly in SCID mice.2. Experimental toxicology and therapy in human tissues.Human skin transplanted to the SCID mice were exposed to ultraviolet light B (UVB) for long period. UVB doses more than 5 x 10^5J/m^2 induced actinic keratosis in 75% of transplanted human skin. Human skin which were more sensitives for keratosis induction were also sensitive to UVB for cancer induction. Daily UVB doses more than 2,000 J/m^2 for 2 years (about 2 x 10^6 J/m^2 in total) induced 3 squqamous cell carcinomas in human skin. It was also possible to treat psoriasis and alopecia skin with human lymphocytes.

为了研究重度联合免疫缺陷小鼠（SCID）长期维持的人体器官和组织的发育、形态、生理和紊乱，我们建立了一套实验系统。人体正常组织的长期维护和功能的检查。改良SCID小鼠的正常人体器官和组织（骨髓、皮肤、甲状腺、结肠、胃、肝、肺、胎儿组织等）维持2-3年。这些人体器官表现出正常的形态和功能。特别是，甲状腺功能通过促甲状腺激素（TSH）治疗保持活跃。在SCID小鼠中，通过注射人TSH使标记碘更活跃地进入人甲状腺。SCID小鼠的人胚胎组织发育良好，生长迅速。人体组织的实验毒理学和治疗。将移植到SCID小鼠体内的人皮肤长期暴露在紫外线B （UVB）下。超过5 × 10^5J/m^2的UVB剂量在75%的移植皮肤中引起光化性角化病。对角化病诱导更敏感的人类皮肤对UVB诱导癌症也很敏感。每日UVB剂量超过2,000 J/m^2，持续2年（总计约2 × 10^6 J/m^2），诱发3例人体皮肤鳞状细胞癌。用人淋巴细胞治疗牛皮癣和脱发也是可能的。