Transplantation of alveolar type II cells stimulates lung regeneration during compensatory lung growth in adult rats.
OBJECTIVE
It is controversial whether lung regeneration contributes to compensatory lung growth after pulmonary resection in mature individuals. The objectives of this study were to clarify the molecular mechanisms that regulate the process of compensatory lung growth and investigate the influence of transplantation of lung cells enriched in alveolar type II cells on compensatory lung growth.


METHODS
Serial changes of morphology and gene expression were examined in the remnant right lung after pneumonectomy in adult male Wistar rats. One day after surgery, animals received endotracheal transplants of rat lung cells enriched in alveolar type II cells at a dose of 2.5 × 10(6) cells. Serial morphologic changes were examined in comparison with pneumonectomy alone. Engraftment of lung cells was validated with a sex-mismatch model.


RESULTS
The alveolar density with mean linear intercept was always lower in pneumonectomized rats than in sham surgical controls for 6 months after surgery. Microarray analysis revealed that multiple genes related to proliferation (but not specific alveolar development) were initially up-regulated and then returned to normal after 1 month. In the pneumonectomized rats with transplantation, the alveolar density was equivalent to that in the sham controls. Engraftment of the transplanted cells from male donors in the alveoli of female recipients was proven by detection of Y-chromosome positive cells and quantified by real-time polymerase chain reaction for the Sry gene. This occurred in pneumonectomized rats but not in sham controls.


CONCLUSIONS
We postulate that lung cell transplantation stimulates lung regeneration in the remnant lung after pneumonectomy in mature rats.
Department of General Thoracic Surgery, Graduate School of Medicine, Chiba University, Chiba, Japan. hirow-12@umin.ac.jp
Hironobu
H
Wada
Shigetoshi
S
Yoshida
Hidemi
H
Suzuki
Yuichi
Y
Sakairi
Teruaki
T
Mizobuchi
Daisuke
D
Komura
Yasunori
Y
Sato
Sana
S
Yokoi
Ichiro
I
Yoshino
D000367:Age Factors; D056809:Alveolar Epithelial Cells / Q000637:transplantation*; D000818:Animals; D049109:Cell Proliferation; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation; D008168:Lung / Q000254:growth & development / Q000473:pathology / Q000601:surgery*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D011013:Pneumonectomy; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D060888:Real-Time Polymerase Chain Reaction; D012038:Regeneration / Q000235:genetics; D051876:Sex-Determining Region Y Protein / Q000235:genetics; D013997:Time Factors; D014998:Y Chromosome
D012333:RNA, Messenger; D051876:Sex-Determining Region Y Protein; C497747:Sry protein, rat