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

IF 3.5 3区环境科学与生态学 Q3 CELL & TISSUE ENGINEERING Regenerative Therapy Pub Date : 2025-03-01 Epub Date: 2025-01-17 DOI:10.1016/j.reth.2025.01.012

Hiroaki Shidei , Ryo Takagi , Shota Mitsuboshi , Hidekazu Sekine , Tatsuya Shimizu , Masato Kanzaki

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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.

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同种异体成纤维细胞片在不粘附胸壁的情况下预防大鼠胸膜缺损引起的肺漏气。

肺漏气是胸外科手术的并发症之一，是肺切除术或胸膜粘连脱离术后不可避免的问题。应用聚乙二醇酸（PGA）片封闭PAL的常规方法容易导致胸膜粘连。本研究评估了同种异体成纤维细胞片移植预防pal的能力。方法：利用表达绿色荧光蛋白（GFP）的转基因大鼠制备成纤维细胞，并在温度敏感培养皿上培养成纤维细胞片。将同种异体成纤维细胞片或PGA片移植到F344/NJcl-rnu/rnu（胸腺肥大大鼠）、Slc:SD （SD）和BN/SsNSlc （BN）大鼠的左肺胸膜缺损上，评估PAL和粘连的预防效果。组织学和免疫学分析评价成纤维细胞或PGA片移植的PALs肺组织。结果：成纤维细胞片和PGA片在所有模型大鼠胸膜缺损中均具有闭合性。移植PGA片的大鼠模型大部分出现粘连，而移植成纤维细胞片的大鼠模型未见粘连。HBME-1免疫染色显示，移植后2周和3个月，成纤维细胞片在无粘连缺陷的胸膜上再生。结论：与自体成纤维细胞片移植相似，同种异体成纤维细胞片移植可预防pal和关闭胸膜缺损，内脏胸膜与胸膜壁层之间无粘连。因此，同种异体成纤维细胞片可作为预防术后PALs的即食密封剂。

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来源期刊

Regenerative Therapy Engineering-Biomedical Engineering

CiteScore

6.00

自引率

2.30%

发文量

106

审稿时长

49 days

期刊介绍： Regenerative Therapy is the official peer-reviewed online journal of the Japanese Society for Regenerative Medicine. Regenerative Therapy is a multidisciplinary journal that publishes original articles and reviews of basic research, clinical translation, industrial development, and regulatory issues focusing on stem cell biology, tissue engineering, and regenerative medicine.