Implantation of fetal rat lung fragments into bleomycin-induced pulmonary fibrosis.
OBJECTIVE
Pulmonary fibrosis is a life-threatening disease that results in progressive respiratory failure. We have suggested the possibility of fetal lung tissue as an option for further investigation into lung regeneration. The objective was to prove whether fetal lung fragments can survive and differentiate in fibrotic lung.


METHODS
Lewis rats were administered bleomycin and used as recipients after 3 or 4 weeks. Day 17 fetal lung tissue from green fluorescent protein Lewis rats was used as donor material. Donor lungs were removed, cut into small pieces, and implanted into the recipients' left lung. The recipients received cyclosporin to prevent immune response to green fluorescent protein and were killed after 1, 2, 4, 8, and 12 weeks and histologically evaluated. Furthermore, the expression of thyroid transcription factor-1 and Clara cell secretory protein in the implanted fetal lung tissue was immunohistologically evaluated.


RESULTS
Fibrotic changes were recognized for a long period of time in the recipient lungs. The implanted fetal lung fragments could be clearly distinguished from recipient lungs because of the luminescence of grafts. Fetal lung fragments could survive in the recipient lungs with fibrotic changes. The air spaces of implanted fetal lungs were narrow at 1 and 2 weeks but expanded with the passage of time. The connection between the recipient lung and the implanted fetal lung was recognized, particularly in the peripheral grafts. The expression patterns of thyroid transcription factor-1 and Clara cell secretory protein in implanted lungs resembled those in the process of normal lung morphogenesis.


CONCLUSIONS
Fetal rat lung fragments could survive and differentiate in bleomycin-induced completely fibrotic lung.
Department of Thoracic and Endocrine Surgery, The University of Tokushima, Kuramoto-cho, Tokushima, Japan.
Hiroaki
H
Toba
Shoji
S
Sakiyama
Koichiro
K
Kenzaki
Yukikiyo
Y
Kawakami
Koh
K
Uyama
Yoshimi
Y
Bando
Akira
A
Tangoku
D000818:Animals; D030801:Animals, Genetically Modified; D001761:Bleomycin; D002454:Cell Differentiation; D004195:Disease Models, Animal; D005260:Female; D006085:Graft Survival; D049452:Green Fluorescent Proteins / Q000096:biosynthesis / Q000235:genetics; D007150:Immunohistochemistry; D008168:Lung / Q000196:embryology / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D016040:Lung Transplantation; D008297:Male; D009687:Nuclear Proteins / Q000378:metabolism; D011658:Pulmonary Fibrosis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D051381:Rats; D011917:Rats, Inbred Lew; D012038:Regeneration; D000074482:Thyroid Nuclear Factor 1; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014598:Uteroglobin / Q000378:metabolism
C000614416:Nkx2-1 protein, rat; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; D001761:Bleomycin; D049452:Green Fluorescent Proteins; D014598:Uteroglobin