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Blood, 1 February 2004, Vol. 103, No. 3, pp. 860-867.
Prepublished online as a Blood First Edition Paper on October 2, 2003; DOI 10.1182/blood-2003-04-1160.

Submitted April 14, 2003
Accepted September 17, 2003
Development of both human connective tissue-type and mucosal-type mast cells in mice from hematopoietic stem cells with identical distribution pattern to human body
Naotomo Kambe, Hidefumi Hiramatsu, Mika Shimonaka, Hisanori Fujino, Ryuta Nishikomori, Toshio Heike, Mamoru Ito, Kimio Kobayashi, Yoshito Ueyama, Norihisa Matsuyoshi, Yoshiki Miyachi, and Tatsutoshi Nakahata*
Department of Pediatrics, Kyoto University, Kyoto, Japan
Department of Dermatology, Kyoto University, Kyoto, Japan
Central Institute for Experimental Animals, Kawasaki, Japan
Department of Pathology, Tokai University, Isehara, Japan
* Corresponding author; email: tnakaha{at}kuhp.kyoto-u.ac.jp.
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 underwent human hematopoietic stem cell transplantation have not been reported. Here we reported on human mast cell development after xenotransplantation of human hematopoietic stem cells into NOD/SCID/ cnull (NOG) mice with severe combined immunodeficiency and IL-2 receptor -chain allelic mutation. Supported by the murine environment, human mast cell clusters developed in mouse dermis, but 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 high effective model for the investigation of human mast cell development and function in vivo.

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