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American Journal of Respiratory Cell and Molecular Biology. Vol. 28, pp. 673-681, 2003
© 2003 American Thoracic Society
DOI: 10.1165/rcmb.2002-0214OC

The Kinetics and Pattern of Tracheal Allograft Re-Epithelialization

Eric M. Genden, Andrew Iskander, Jonathan S. Bromberg and Lloyd Mayer

Departments of Otolaryngology-Head and Neck Surgery, Surgery and The Institute for Gene Therapy and Molecular Medicine, and The Immunobiology Center, The Mount Sinai School of Medicine, New York, New York

Address correspondence to: Eric M. Genden, M.D., Mount Sinai School of Medicine, Department of Otolaryngology-Head and Neck Surgery, One Gustave Levy Place, New York, NY 10029. E-mail: eric.genden{at}mssm.edu

Extensive tracheal defects may pose a life-threatening dilemma. Although tracheal transplantation may represent a reconstructive solution, very little is known regarding the immunobiology and behavior of tracheal allografts. The objective of this study was to assess the pattern and kinetics of re-epithelialization of orthotopic tracheal allografts in immunosuppressed recipients. Thirty-eight age-matched mice were randomly assigned to five experimental groups. BALB/c donor tracheal segments were orthotopically transplanted into either syngeneic BALB/c or MHC mismatched allogeneic C57BL/6 recipients with and without immunosuppression. On post-transplant days 7, 14, 28, 48, and 62, animals from each group were evaluated by serial histology, electron microscopy, and serial immunohistochemical analysis for mucosal phenotype, re-epithelialization pattern, and lymphocyte subpopulations. Nonimmunosuppressed recipients underwent recipient-derived basal cell re-epithelialization by Day 48, with differentiation into a sparse population of ciliated columnar epithelium by Day 62, whereas immunosuppressed recipients underwent basal cell re-epithelialization 28 d after transplantation and differentiation into a dense population of ciliated columnar epithelium by Day 48. The re-epithelialization process occurred in a definable pattern that was significantly enhanced with the addition of immunosuppression. Orthotopic tracheal transplants undergo progressive re-epithelialization with recipient-derived basal cells that differentiate into ciliated columnar epithelium in a definable pattern that is enhanced with the addition of immunosuppression.

Abbreviations: cyclosporine A, CsA • ketamine and xylazine anesthesia, KA • ratio of the lamina propria to the tracheal cartilage, LCR • phosphate-buffered saline, PBS




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