Kambe Naotomo, Hiramatsu Hidefumi, Shimonaka Mika, Fujino Hisanori, Nishikomori Ryuta, Heike Toshio, Ito Mamoru, Kobayashi Kimio, Ueyama Yoshito, Matsuyoshi Norihisa, Miyachi Yoshiki, Nakahata Tatsutoshi
Department of Pediatrics, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Blood. 2004 Feb 1;103(3):860-7. doi: 10.1182/blood-2003-04-1160. Epub 2003 Oct 2.
The transplantation of primitive human cells into sublethally irradiated immune-deficient mice is the well-established in vivo system for the investigation of human hematopoietic stem cell function. Although mast cells are the progeny of hematopoietic stem cells, human mast cell development in mice that underwent human hematopoietic stem cell transplantation has not been reported. Here we report on human mast cell development after xenotransplantation of human hematopoietic stem cells into nonobese diabetic severe combined immunodeficient (NOD/SCID)/gamma(c)(null) (NOG) mice with severe combined immunodeficiency and interleukin 2 (IL-2) receptor gamma-chain allelic mutation. Supported by the murine environment, human mast cell clusters developed in mouse dermis, but they required more time than other forms of human cell reconstitution. In lung and gastric tract, mucosal-type mast cells containing tryptase but lacking chymase located on gastric mucosa and in alveoli, whereas connective tissue-type mast cells containing both tryptase and chymase located on gastric submucosa and around major airways, as in the human body. Mast cell development was also observed in lymph nodes, spleen, and peritoneal cavity but not in the peripheral blood. Xenotransplantation of human hematopoietic stem cells into NOG mice can be expected to result in a highly effective model for the investigation of human mast cell development and function in vivo.
将原始人类细胞移植到经亚致死剂量照射的免疫缺陷小鼠体内，是用于研究人类造血干细胞功能的成熟体内系统。尽管肥大细胞是造血干细胞的后代，但尚未有关于接受人类造血干细胞移植的小鼠中人类肥大细胞发育的报道。在此，我们报告了将人类造血干细胞异种移植到具有严重联合免疫缺陷和白细胞介素2（IL-2）受体γ链等位基因突变的非肥胖糖尿病严重联合免疫缺陷（NOD/SCID）/γ(c)(null)（NOG）小鼠后人类肥大细胞的发育情况。在小鼠环境的支持下，人类肥大细胞簇在小鼠真皮中形成，但它们比其他形式的人类细胞重建需要更多时间。在肺和胃肠道中，黏膜型肥大细胞含有类胰蛋白酶但缺乏胃黏膜和肺泡中的糜蛋白酶，而结缔组织型肥大细胞同时含有类胰蛋白酶和糜蛋白酶，位于胃黏膜下层和主要气道周围，与人体情况相同。在淋巴结、脾脏和腹腔中也观察到了肥大细胞的发育，但在外周血中未观察到。将人类造血干细胞异种移植到NOG小鼠体内有望成为一种在体内研究人类肥大细胞发育和功能的高效模型。
