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.
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.
Kambe
Naotomo
N
Department of Pediatrics, Kyoto University Graduate School of Medicine, 54 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Hiramatsu
Hidefumi
H
Shimonaka
Mika
M
Fujino
Hisanori
H
Nishikomori
Ryuta
R
Heike
Toshio
T
Ito
Mamoru
M
Kobayashi
Kimio
K
Ueyama
Yoshito
Y
Matsuyoshi
Norihisa
N
Miyachi
Yoshiki
Y
Nakahata
Tatsutoshi
T
D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D053818:Chymases; D003239:Connective Tissue Cells / Q000166:cytology* / Q000378:metabolism; D018076:DNA, Complementary / Q000235:genetics; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D006801:Humans; D008407:Mast Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D008817:Mice, Mutant Strains; D016513:Mice, SCID; D009092:Mucous Membrane / Q000166:cytology* / Q000378:metabolism; D009928:Organ Specificity; D015375:Receptors, Interleukin-2 / Q000172:deficiency / Q000235:genetics; D012697:Serine Endopeptidases / Q000378:metabolism; D019089:Stem Cell Factor / Q000096:biosynthesis; D014183:Transplantation, Heterologous; D053802:Tryptases
D018076:DNA, Complementary; D015375:Receptors, Interleukin-2; D019089:Stem Cell Factor; C509190:Tpsb2 protein, mouse; D012697:Serine Endopeptidases; D053818:Chymases; C509222:Tpsab1 protein, mouse; D053802:Tryptases