Transplanted Fibroblasts Proliferate in Host Bronchial Tissue and Enhance Bronchial Anastomotic Healing in a Rodent Model

Abstract

Introduction

Healing of airway anastomoses after preoperative irradiation can be a significant clinical problem. The augmentation of bronchial anastomoses with a fibroblast-seeded human acellular dermis (hAD) was shown to be beneficial, although the underlying mechanism remained unclear. Therefore, in this study we investigated the fate of the fibroblasts transplanted to the scaffold covering the anastomosis.

Material and methods

32 Fisher rats underwent surgical anastomosis of the left main bronchus. In a 2 × 2 factorial design, they were randomized to receive preoperative irradiation of 20 Gy and augmentation of the anastomosis with a fibroblast-seeded transplant. Fibroblasts from subcutaneous fat of Fischer-344 rat were transduced retrovirally with tdTomato for cell tracking. After 7 and 14 days, animals were sacrificed and cell concentration of transplanted and nontransplanted fibroblasts in the hAD as well as in the bronchial tissue was measured using RT-PCR.

Results

Migration of transplanted fibroblasts from dermis to bronchus were demonstrated in both groups, irradiated and nonirradiated. In the irradiated groups, there was a cell count of 7 × 10⁴ ± 1 × 10⁴ tomato⁺-fibroblasts in the bronchial tissue at day 7, rising to 1 × 10⁵ ± 1 × 10⁴ on day 14 (p<0.0001). Tomato⁺-cell concentration in hAD increased from 6 × 10³ ± 1 × 10³ at day 7 to 6 × 10⁴ ± 1 × 10⁴ at day 14 (p<0.0001). In the nonirradiated groups, tomato⁺-cell concentration in bronchus was 4 × 10³ ± 1 × 10³ on day 7 and 4 × 10³ ± 1 × 10³ at day 14. In the hAD tomato⁺ cell concentration rising from 1 × 10⁴ ± 1 × 10³ at day 7 to 2 × 10⁴ ± 3 × 10³ cells at day 14 (p = 0.0028).

Conclusions

Transplanted fibroblasts in the irradiated groups proliferate and migrate into the irradiated host bronchial tissue, but not in the nonirradiated groups.