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

我们建立了一套实验系统来研究长期维持在严重联合免疫缺陷小鼠(SCID)体内的人体器官和组织的发育、形态、生理和紊乱情况。人体正常组织的长期维护和功能检查。人体正常器官和组织(骨髓、皮肤、甲状腺、结肠、胃、肝脏、肺、胎儿组织等)在改良的SCID小鼠中维持2-3年。这些人体器官表现出正常的形态和功能。尤其是促甲状腺激素(TSH)治疗后，甲状腺功能保持活跃。通过向SCID小鼠注射人TSH，标记的碘被掺入到人的甲状腺中，在SCID小鼠体内的维持更为活跃。人胚胎组织在SCID小鼠体内发育良好，生长迅速。人皮肤移植到SCID小鼠体内，长期暴露于紫外线B(UVB)中。大于5×10~(-5)J/m~(-2)的UVB剂量可引起75%的人移植皮肤光化性角化。人体皮肤对角化病的诱发更敏感，对UVB的致癌作用也更敏感。UVB辐射剂量超过2,000J/m^2，持续2年(总计约2×10~6J/m~2)可诱发3例人皮肤鳞状细胞癌。用人类淋巴细胞治疗牛皮癣和脱发皮肤也是可能的。

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.