Orthotopic tracheal transplantation in the murine model.

Abstract

Before tracheal transplantation can be clinically applied for the reconstruction of life-threatening airway defects, the immunobiology of this organ system must be better characterized. The availability of reagents and transgenic mice strains make the murine model ideal for this purpose. We have developed a reliable and reproducible method of orthotopic tracheal transplantation and characterized the kinetics of rejection. Balb/c donor tracheal segments (five tracheal rings), were orthotopically transplanted into either syngeneic Balb/c recipients or allogeneic C57BL/6 recipients. Tracheal graft rejection was monitored by daily clinical airway assessment, in vivo cilia motility, and histologic examination using hematoxylin and eosin staining and CD8/CD4 immunohistochemistry. Two days after tracheal transplantation, allogenic recipients developed a persistent audible stridor that did not occur in the syngeneic experimental group. Whereas syngeneic tracheal autografts demonstrated normal mucociliary function after transplantation, allogeneic recipients failed to achieve normal mucociliary function. Normal histologic architecture persisted in the syngeneic grafts without evidence of lymphocytic infiltrate; however, the nonimmunosuppressed allogeneic grafts demonstrated a loss of normal ciliated respiratory epithelia and a CD8/CD4-positive lymphocytic infiltrate that peaked at 21 days after transplantation. The Balb/c (donor) to C57BL/6 (recipient) murine orthotopic tracheal transplant model offers a reliable method for the study of tracheal transplantation.