Lung regeneration : implantation of fetal rat lung fragments into adult rat lung with bleomycine induced fibrosis

2006 Fiscal Year Final Research Report Summary

• Project/Area Number: 17591474
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: The University of Tokushima
• Principal Investigator: SEKIYAMA Syoji The University of Tokushima, Institute of Health Biosciences, Senior assistant Professor, 大学院ヘルスバイオサイエンス研究部, 講師 (60291986)
• Co-Investigator(Kenkyū-buntansha): KONDO Kazuya The University of Tokushima, Tokushima University Hospital, Senior assistant Professor, 医学部・歯学部附属病院, 講師 (10263815) ; MIYOSHI Takanori The University of Tokushima, Tokushima University Hospital, Senior assistant Professor, 医学部・歯学部附属病院, 講師 (20346612) ; KENZAKI Koichiro The University of Tokushima, Tokushima University Hospital, Assistant Professor, 医学部・歯学部附属病院, 助手 (70325265) ; YOSHIDA Mitsuteru The University of Tokushima, Tokushima University Hospital, medical doctor, 医学部・歯学部附属病院, 医員 (30403710) ; TOBA Hiroaki The University of Tokushima, Tokushima University Hospital, medical doctor, 医学部・歯学部附属病院, 医員 (40403745)
• Project Period (FY): 2005 – 2006
• Keywords: lung regeneration / lung / rat / fetal lung tissue / fetal lung / transplantation / pulmonary fibrosis / bleomycine

Research Abstract

We previously reported that normal fetal lung tissues could survive and further grow and differentiate inside normal adult lung (J Thorac Cardiovasc Surg 2006; 131; 1148-53). In the present study, normal fetal lung tissues were implanted to bleomycine induced fibrotic adult rat lung parenchyma. GFP-LEW fetal lung tissues (day 17) were used as a donor. Normal adult rats were treated with intratracheal administration of bleomycine via a fine catheter to cause a situation of pulmonary fibrosis. A catheter (tracheotomy tube) was implanted in each rat three days before dosing. Bleomycine at a total dose of 4.5mg/kg or 3mg/kg was administered in four divided doses. Saline was administered for control rats.
Day 17 fetal rat lungs tissues (GFP positive) in culture medium implanted to adult rats treated with bleomycine 3 or 4 weeks ago. To suppress immune responses to GFP antigen, recipient rats were administrated cyclosporine (10mg/kg i.m. on alternate days from day 0, dose of cyclosporine was decrease gradually). Recipient rats were killed 1, 2, 4, 8, 12 weeks after implantation. Recipient lungs implanted with fetal lung tissues were serially cut and examined under fluorescence microscope. The same specimens were stained with hematoxylin and eosin.
The grafts implanted into pulmonary parenchyma with bleomycine induced fibrosis could survive and grow and differentiated with opening of the alveolar space.