Implantation of fetal rat lung fragments

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.


 see the original article on the potential of lung fragments


Hiroaki Toba, MD^a, Shoji Sakiyama, MD, PhD^a,_*, Koichiro Kenzaki, MD, PhD^a, Yukikiyo Kawakami, MD^a, Koh Uyama, MD^a, Yoshimi Bando, MD, PhD^b, Akira Tangoku, MD, PhD^a
 
a Department of Thoracic and Endocrine Surgery and Oncology, The University of Tokushima, Kuramoto-cho, Tokushima, Japan
^b Department of Molecular and Environmental Pathology, Institute of Health Biosciences, The University of Tokushima, Kuramoto-cho, Tokushima, Japan
Received for publication November 4, 2011; revisions received December 13, 2011; accepted for publication January 4, 2012.
_^* Address for reprints: Shoji Sakiyama, MD, PhD, Department of Thoracic and Endocrine Surgery and Oncology, Institute of Health Biosciences, The University of Tokushima, Kuramoto-cho, Tokushima 770-8503, Japan. (Email: sakiyama@clin.med.tokushima-u.ac.jp ).