Engraftment of adult human lung tissue in nonobese diabetic/severe combined immunodeficient mice: a novel lung epithelial regeneration model.
OBJECTIVE
Injury causes the disruption of homeostatic cell-cell interactions and epithelial regeneration is part of the threshold response. Due to the lack of a good animal model for the investigation of these mechanisms, the kinetics of cell proliferation after injury to the human respiratory tract are poorly understood.


METHODS
To create a better model of human bronchioloalveolar epithelial regeneration, we engrafted adult human lung tissue into nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice. Then the lung tissue was studied at various times up to 20 weeks after implantation.


RESULTS
The xenografts of bronchiolar epithelium showed characteristic features, including positivity for specific human antigens, and extensive regeneration was observed within 8 weeks after implantation. In addition, a few alveolar type II epithelial cells expressing prosurfactant protein C were detected in some areas. The distal alveolar spaces were filled with protein-rich material and were markedly dilated. Abundantly ciliated secretory epithelium, which was similar to normal adult bronchiolar epithelium, was observed within 16 weeks after implantation in the mice. All of the human lung tissue specimens that were implanted subcutaneously into the backs of the mice developed well and remained viable for 20 weeks. Each type of adult human lung epithelial cell showed a different mode of proliferation. Bronchiolar epithelial cells proliferated earlier, with MIB-1 labeling of up to 20% of the cells in the grafts at 8 weeks, while alveolar type II cells proliferated later, with labeling of up to 5% of graft cells at 12 weeks.


CONCLUSIONS
This model seems to allow adult human lung epithelial regeneration to be investigated in vivo over the long term.
Yonou
Hiroyuki
H
Pathology Division, National Cancer Center Research Institute East, Chiba, Germany.
Yokose
Tomoyuki
T
Yoshikawa
Takeshi
T
Kanomata
Naoki
N
Kamijo
Tomoyuki
T
Hasebe
Takahiro
T
Nagai
Kanji
K
Ito
Hiroshi
H
Yamasaki
Akira
A
Hatano
Tadashi
T
Ogawa
Yoshihide
Y
Emura
Makito
M
Ochiai
Atsushi
A
D000368:Aged; D000818:Animals; D002455:Cell Division; D004848:Epithelium / Q000502:physiology* / Q000648:ultrastructure; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D016040:Lung Transplantation / Q000502:physiology*; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008854:Microscopy, Electron; D008875:Middle Aged; D023421:Models, Animal; D012038:Regeneration; D014183:Transplantation, Heterologous; D019737:Transplants