Abstract
Human tracheal disorders severely compromise a patient’s quality of life and can be life threatening. Ex vivo tracheal reconstruction using biological or a bioartificial composite scaffolds recellularized with autologous cells have been performed in first-in-human studies in other countries based on compassionate use. However, there are outstanding scientific questions that must be answered before human clinical trials can be considered in the U.S. The objective of this study was to determine if buccal biopsies could serve as a source of autologous epithelial cells for tracheal tissue engineering. We hypothesized that epithelial cells obtained from the buccal mucosa would share similar characteristics with epithelial cells obtained from airways and could be used as an alternative epithelial cell source for tracheal tissue engineering. In Specific Aim 1 immunohistochemistry and quantitative PCR was used to compare the native protein and gene expression patterns in buccal mucosa epithelium, trachea, and airway bronchus in the rhesus monkey, a species with many similarities in anatomy and cell-based features when compared to humans. Specific Aim 2 was focused on investigating and optimizing cell culture techniques for buccal epithelial cell isolation, using clinically translatable methods. The results of these in vitro studies provide insights into the culture conditions needed for the proliferation of autologous buccal cells for use in tissue engineering of a tracheal construct for transplant into humans. This project was completed at UC Davis and will contribute to a larger funded project investigating the safety and efficacy of stem cell-derived, tissue-engineered airway implants for long-segment airway disorders.