Transplantation of alveolar type II cells stimulates lung regeneration during compensatory lung growth in adult rats

Hironobu Wada, Shigetoshi Yoshida, Hidemi Suzuki, Yuichi Sakairi, Teruaki Mizobuchi, Daisuke Komura, Yasunori Sato, Sana Yokoi, Ichiro Yoshino

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

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.

Original languageEnglish
JournalJournal of Thoracic and Cardiovascular Surgery
Volume143
Issue number3
DOIs
Publication statusPublished - 2012 Jan 1
Externally publishedYes

Fingerprint

Alveolar Epithelial Cells
Regeneration
Transplantation
Lung
Growth
Pneumonectomy
Lung Transplantation
Cell Transplantation
sry Genes
Y Chromosome
Microarray Analysis
Ambulatory Surgical Procedures
Wistar Rats
Real-Time Polymerase Chain Reaction
Transplants

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

Cite this

Transplantation of alveolar type II cells stimulates lung regeneration during compensatory lung growth in adult rats. / Wada, Hironobu; Yoshida, Shigetoshi; Suzuki, Hidemi; Sakairi, Yuichi; Mizobuchi, Teruaki; Komura, Daisuke; Sato, Yasunori; Yokoi, Sana; Yoshino, Ichiro.

In: Journal of Thoracic and Cardiovascular Surgery, Vol. 143, No. 3, 01.01.2012.

Research output: Contribution to journalArticle

Wada, Hironobu ; Yoshida, Shigetoshi ; Suzuki, Hidemi ; Sakairi, Yuichi ; Mizobuchi, Teruaki ; Komura, Daisuke ; Sato, Yasunori ; Yokoi, Sana ; Yoshino, Ichiro. / Transplantation of alveolar type II cells stimulates lung regeneration during compensatory lung growth in adult rats. In: Journal of Thoracic and Cardiovascular Surgery. 2012 ; Vol. 143, No. 3.
@article{85e83242332c4d3fbad5ff12122475f7,
title = "Transplantation of alveolar type II cells stimulates lung regeneration during compensatory lung growth in adult rats",
abstract = "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.",
author = "Hironobu Wada and Shigetoshi Yoshida and Hidemi Suzuki and Yuichi Sakairi and Teruaki Mizobuchi and Daisuke Komura and Yasunori Sato and Sana Yokoi and Ichiro Yoshino",
year = "2012",
month = "1",
day = "1",
doi = "10.1016/j.jtcvs.2011.09.024",
language = "English",
volume = "143",
journal = "Journal of Thoracic and Cardiovascular Surgery",
issn = "0022-5223",
publisher = "Mosby Inc.",
number = "3",

}

TY - JOUR

T1 - Transplantation of alveolar type II cells stimulates lung regeneration during compensatory lung growth in adult rats

AU - Wada, Hironobu

AU - Yoshida, Shigetoshi

AU - Suzuki, Hidemi

AU - Sakairi, Yuichi

AU - Mizobuchi, Teruaki

AU - Komura, Daisuke

AU - Sato, Yasunori

AU - Yokoi, Sana

AU - Yoshino, Ichiro

PY - 2012/1/1

Y1 - 2012/1/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84857232427&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84857232427&partnerID=8YFLogxK

U2 - 10.1016/j.jtcvs.2011.09.024

DO - 10.1016/j.jtcvs.2011.09.024

M3 - Article

VL - 143

JO - Journal of Thoracic and Cardiovascular Surgery

JF - Journal of Thoracic and Cardiovascular Surgery

SN - 0022-5223

IS - 3

ER -