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

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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.