A Heterotopic Mouse Model for Studying Laryngeal Transplantation

Maeve M. Kennedy; Egehan Salepci; Cheryl Myers; Marshall Strome; David G. Lott

doi:10.3791/63619

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Method Article

A Heterotopic Mouse Model for Studying Laryngeal Transplantation

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DOI:

10.3791/63619

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January 13th, 2023

Maeve M. Kennedy^*¹ , Egehan Salepci^*¹^,² , Cheryl Myers¹ , Marshall Strome³^,⁴ , David G. Lott¹^,⁵

¹Head and Neck Regenerative Medicine Laboratory, Center for Regenerative Medicine, Mayo Clinic Arizona, ²Department of Otorhinolaryngology, University of Health Sciences, Sisli Hamidiye Etfal Training and Research Hospital, ³Department of Otolaryngology, Vanderbilt University, ⁴Cleveland Clinic Head and Neck Institute, ⁵Division of Laryngology, Department of Otolaryngology Head and Neck Surgery, Mayo Clinic Arizona

^* These authors contributed equally

Summary

The aim of this manuscript is to describe the microsurgical steps required to perform a heterotopic laryngeal transplant in mice. The advantages of this mouse model compared to other animal models of laryngeal transplantation are its cost-effectiveness and the availability of immunologic assays and data.

Abstract

Laryngeal heterotopic transplantation, although a technically challenging procedure, offers more scientific analysis and cost benefits compared to other animal models. Although first described by Shipchandler et al. in 2009, this technique is not widely used, possibly due to the difficulties in learning the microsurgical technique and time required to master it. This paper describes the surgical steps in detail, as well as potential pitfalls to avoid, in order to encourage effective use of this technique.

In this model, the bilateral carotid arteries of the donor larynx are anastomosed to the recipient carotid artery and external jugular vein, allowing for blood flow through the graft. Blood flow can be confirmed intraoperatively by the visualization of blood filling in the graft bilateral carotid arteries, reddening of the thyroid glands of the graft, and bleeding from micro vessels in the graft. The crucial elements for success include delicate preservation of the graft vessels, making the correct size arteriotomy and venotomy, and using the appropriate number of sutures on the arterial-arterial and arterial-venous anastomoses to secure vessels without leakage and prevent occlusion.

Anyone can become proficient in this model with sufficient training and perform the procedure in approximately 3 h. If performed successfully, this model allows for immunologic studies to be performed with ease and at low cost.

Introduction

For patients suffering from irreparable laryngeal damage or laryngeal cancer, a total laryngectomy is often the only option¹. Total laryngectomy leaves patients without the ability to breathe and speak on their own, in addition to experiencing social and psychological distress². Patients with laryngeal cancer who need a total laryngectomy are excellent potential candidates for laryngeal transplantation. While human laryngeal transplantation in the setting of irreparable laryngeal damage has been performed, allotransplantation of the larynx is currently avoided in these patients due to the fear of tumor recurrence, the po....