Case Report: Human Tracheal Transplantation Undergoes Progressive Reepithelialization Over Time.

OBJECTIVES: Tracheal transplantation is an ideal option for the reconstruction of long-segment circumferential tracheal defects. Our group performed the first successful vascularized single-staged tracheal transplantation in January 2021. Although a rigid biocompatible structure is necessary for a functioning tracheal replacement, the importance of ciliated epithelium, which allows for critical mucociliary clearance, is now being appreciated. Here, we examined the histological changes of the first single-staged human tracheal transplant from serial endoscopic biopsies. METHODS: Biopsies of the tracheal mucosa were serially obtained since the time of the tracheal transplantation. Samples were examined via hematoxylin and eosin, electron microscopy, and immunohistochemistry. RESULTS: One week after transplantation, there is loss of ciliated epithelium and seromucinous cells, with only a basal layer of epithelium remaining. By 2 weeks, however, the epithelium begins to recover, albeit differently depending on the location of the biopsy. Near the site of tracheal anastomosis, there is epithelial proliferation, with the appearance of early ciliated cells. However, in the midgraft, there appears to be evidence of squamous metaplasia. Over time, however, normal ciliated epithelium and mucous cells appear without signs of chronic inflammation. CONCLUSIONS: Critically, the tracheal allograft regained normal appearing respiratory epithelium after initial ischemic injury. The histologic differences at the midgraft versus anastomosis may suggest unique mechanisms of reepithelialization. At the recipient-donor interface, there may be a faster direct migration of recipient-derived epithelial cells, in line with preclinical studies. The midgraft, in contrast, responds with epithelial proliferation from the donor basal cells or dedifferentiated mucous cells. LEVEL OF EVIDENCE: N/A Laryngoscope, 2023.