Laryngeal Tissue Engineering Using Rabbit Adipose Derived Stem Cells in Fibrin: A Pre-clinical Model - Laryngeal Tissue Engineering Using Rabbit Adipose Derived Stem Cells in Fibrin: A Pre-clinical Model - Open Access Pub

Vocal fold scarring is a clinical problem without reliable treatment. Tissue engineering of a vocal fold replacement is an exciting potential treatment for vocal fold scars that involve multiple layers of the vocal fold. Human adipose-derived stem cells (ASC) were previously used to produce a promising vocal fold cover layer replacement. However, relevant in vivo studies are needed before human application, and implanting the human cells in animal larynges would introduce significant risk and data confounding. We therefore report here the development of a construct based on rabbit ASC with the potential for use in pre-clinical implantation studies. Rabbit ASC were isolated and cultured in a three-dimensional fibrin matrix to create an implantable construct resembling the vocal fold mucosa. Key differences between the human cell and the rabbit cell models are highlighted. DOI 10.14302/issn.2379-8572.joa-14-611 Translating in vitro models into pre-clinical development is a significant hurdle in the advancement of tissue-engineered therapies. Potential therapies are typically developed in vitro, and then must be vetted in a relevant animal model before beginning human clinical trials. For tissue-engineered organ replacements, this means developing a species-specific implant. Construct design for preclinical animal trials may differ from both the initial in vitro product and the eventual human implant. For example, tissue engineering of a vocal fold replacement is an exciting potential treatment for vocal fold scars that impair vibration and cause voice disturbance. Few reliable options currently exist to improve the dysphonia1, 2, 3, 4. This laboratory has developed a cell-populated three-dimensional tissue-engineered construct intended for vocal fold cover layer replacement5. Human adipose-derived stem cells (ASC) embedded within a clotted cryoprecipitate scaffold differentiate into a bilayered construct intended for vocal fold cover replacement5. This model shows promising function in vitro as a replacement for the vibratory lamina propria and epithelial layers6. An advantage of the design is its composition from all potentially autologous sources. While this model is appealing for human use, it requires adaptation for pre-clinical studies in animals. The vocal folds are exquisitely sensitive to scar formation, and the immune response expected from the xenograft implant of human cells or scaffold may significantly confound their wound healing. In this work, we set out to develop a tissue-engineered construct suitable for implantation in rabbit vocal