Allogeneic fibroblast sheets prevent pulmonary air leaks caused by rat pleural defects without adhesion to the thoracic wall

Abstract

Introduction

Pulmonary air leak (PAL) is one of a complication of thoracic surgery and an unavoidable problem after lung resection or pleural adhesion detachment. Conventional procedures to close PAL by applying polyglycolic acid (PGA) sheets are prone to pleural adhesion. This study evaluated the ability of allogeneic fibroblast sheet transplantation to prevent PALs.

Methods

Rat skin fibroblasts were prepared from transgenic rats expressing green fluorescent protein (GFP) and cultured on temperature-responsive culture dishes to harvest fibroblast sheets. Allogeneic fibroblast sheets or PGA sheets were transplanted onto the pleural defects of the left lung in F344/NJcl-rnu/rnu (athymic rat), Slc:SD (SD), and BN/SsNSlc (BN) rats to assess PAL and adhesion prevention. Histological and immunological analyses were conducted to evaluate lung tissue of PALs transplanted with fibroblast or PGA sheets.

Results

Fibroblast sheets and PGA sheets closed pleural defects with PALs in all rat models. Adhesions were observed in most rat models transplanted with PGA sheets, but no adhesions were observed in rat models transplanted with fibroblast sheets. Immunostaining for HBME-1 indicated the regeneration of pleura by fibroblast sheet transplantation on the defects without adhesions after 2 weeks and 3 months of transplantation.

Conclusions

Similar to autologous fibroblast sheet transplantation, the transplantation of allogeneic fibroblast sheets prevented PALs and closed pleural defects without adhesion between the visceral and parietal pleura. Therefore, it can be concluded that allogeneic fibroblast sheets can be used as a ready-to-use sealant for preventing postoperative PALs.