Evaluation of Immunosuppressive Therapy Use for Tracheal Transplantation with Trachea-Mimetic Bellows Scaffolds in a Rabbit Model.

Jae Yeon Lee,Gonhyung Kim,Dong-Woo Cho,Jeong Hun Park,Seok Hwa Choi,Mina Han,Seong Soo Kang,Soo Jin Son

doi:10.1155/2017/5205476

Abstract

The objective of this study was to evaluate the use of immunosuppressive therapy with high-dose cyclosporine, high-dose azathioprine, and a combination of low-dose cyclosporine and azathioprine after tracheal reconstruction by using a trachea-mimetic graft of polycaprolactone (PCL) bellows-type scaffold in a rabbit model. Twenty-four healthy New Zealand white rabbits were used in the study. All underwent circumferential tracheal replacement using tissue-engineered tracheal graft, prepared from PCL bellows scaffold reinforced with silicone ring, collagen hydrogel, and human turbinate mesenchymal stromal cell (hTMSC) sheets. The control group (Group 1) received no medication. The three experimental groups were given daily cyclosporine intramuscular doses of 10 mg/kg (Group 2), azathioprine oral doses of 5 mg/kg (Group 3), and azathioprine oral doses of 2.5 mg/kg plus cyclosporine intramuscular doses of 5 mg/kg (Group 4) for 4 weeks or until death. Group 1 had longer survival times compared to Group 2 or Group 3. Each group except for Group 1 experienced decreases in amount of nutrition and weight loss. In addition, compared with the other groups, Group 2 had significantly increased serum interleukin-2 and interferon-γ levels 7 days after transplantation. The results of this study showed that the administration of cyclosporine and/or azathioprine after tracheal transplantation had no beneficial effects. Furthermore, the administration of cyclosporine had side effects, including extreme weight loss, respiratory distress, and diarrhea. Therefore, cyclosporine and azathioprine avoidance may be recommended for tracheal reconstruction using a native trachea-mimetic graft of PCL bellows-type scaffold in a rabbit model.

Highlights

A large-ranging tracheal resection is frequently required in patients with tumours involving the trachea or with benign, congenital, or inflammatory tracheal stenosis [1,2,3,4,5,6]
Some surgical procedures—such as resection with primary anastomosis, slide-tracheoplasty, and costal cartilage tracheoplasty—have been performed, but they have not allowed for the reconstruction of more extensive lesions [7,8,9]
The introduction of cyclosporine in clinical organ transplantation has improved the efficacy of immunosuppressive treatment, leading to a decline in the incidence of acuterejection episodes and allograft loss in the first year after transplantation

Summary

Introduction

A large-ranging tracheal resection is frequently required in patients with tumours involving the trachea or with benign, congenital, or inflammatory tracheal stenosis [1,2,3,4,5,6]. Some surgical procedures—such as resection with primary anastomosis, slide-tracheoplasty, and costal cartilage tracheoplasty—have been performed, but they have not allowed for the reconstruction of more extensive lesions [7,8,9]. Various tracheal substitutes and various techniques of reconstruction have been investigated, including an artificial trachea scaffold, autogenous tissue, and an allotransplant, but resection remains a clinically unsolved surgical and biological problem. Many immunosuppressants have become available or are being investigated for clinical use, none of them is perfect because of their adverse effects.

Objectives

Methods

Conclusion