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

本研究建立了一个研究长期维持的严重联合免疫缺陷小鼠（SCID）体内器官组织发育、形态、生理和功能紊乱的实验体系.正常人体组织的长期维护和功能检查。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）在改良的SCID小鼠中维持2-3年。这些人体器官显示出正常的形态和功能。特别是，通过促甲状腺激素（TSH）治疗，甲状腺功能保持活跃。通过向小鼠注射人TSH，标记碘更积极地掺入SCID小鼠中维持的人甲状腺中。人胚胎组织在SCID小鼠体内发育良好，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于紫外线B（UVB）中。UVB剂量超过5 × 10^5J/m^2时，75%的移植皮肤会出现光化性角化病。对角化病诱导更敏感的人类皮肤也对UVB的癌症诱导敏感。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），在人体皮肤中诱发3例鳞状细胞癌。也有可能用人淋巴细胞治疗牛皮癣和脱发皮肤。

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.