Jennifer L Long1,2. 1. Research Service, Greater Los Angeles VAHS, Los Angeles, California, U.S.A. 2. Department of Head and Neck Surgery, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, California, U.S.A.
Abstract
OBJECTIVE: A vibratory vocal fold replacement would introduce a new treatment paradigm for structural vocal fold diseases such as scarring and lamina propria loss. This work implants a tissue-engineered replacement for vocal fold lamina propria and epithelium in rabbits and compares histology and function to injured controls and orthotopic transplants. Hypotheses were that the cell-based implant would engraft and control the wound response, reducing fibrosis and restoring vibration. STUDY DESIGN: Translational research. METHODS: Rabbit adipose-derived mesenchymal stem cells (ASC) were embedded within a three-dimensional fibrin gel, forming the cell-based outer vocal fold replacement (COVR). Sixteen rabbits underwent unilateral resection of vocal fold epithelium and lamina propria, as well as reconstruction with one of three treatments: fibrin glue alone with healing by secondary intention, replantation of autologous resected vocal fold cover, or COVR implantation. After 4 weeks, larynges were examined histologically and with phonation. RESULTS: Fifteen rabbits survived. All tissues incorporated well after implantation. After 1 month, both graft types improved histology and vibration relative to injured controls. Extracellular matrix (ECM) of the replanted mucosa was disrupted, and ECM of the COVR implants remained immature. Immune reaction was evident when male cells were implanted into female rabbits. Best histologic and short-term vibratory outcomes were achieved with COVR implants containing male cells implanted into male rabbits. CONCLUSION: Vocal fold cover replacement with a stem cell-based tissue-engineered construct is feasible and beneficial in acute rabbit implantation. Wound-modifying behavior of the COVR implant is judged to be an important factor in preventing fibrosis. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:153-159, 2018.
OBJECTIVE: A vibratory vocal fold replacement would introduce a new treatment paradigm for structural vocal fold diseases such as scarring and lamina propria loss. This work implants a tissue-engineered replacement for vocal fold lamina propria and epithelium in rabbits and compares histology and function to injured controls and orthotopic transplants. Hypotheses were that the cell-based implant would engraft and control the wound response, reducing fibrosis and restoring vibration. STUDY DESIGN: Translational research. METHODS:Rabbit adipose-derived mesenchymal stem cells (ASC) were embedded within a three-dimensional fibrin gel, forming the cell-based outer vocal fold replacement (COVR). Sixteen rabbits underwent unilateral resection of vocal fold epithelium and lamina propria, as well as reconstruction with one of three treatments: fibrin glue alone with healing by secondary intention, replantation of autologous resected vocal fold cover, or COVR implantation. After 4 weeks, larynges were examined histologically and with phonation. RESULTS: Fifteen rabbits survived. All tissues incorporated well after implantation. After 1 month, both graft types improved histology and vibration relative to injured controls. Extracellular matrix (ECM) of the replanted mucosa was disrupted, and ECM of the COVR implants remained immature. Immune reaction was evident when male cells were implanted into female rabbits. Best histologic and short-term vibratory outcomes were achieved with COVR implants containing male cells implanted into male rabbits. CONCLUSION: Vocal fold cover replacement with a stem cell-based tissue-engineered construct is feasible and beneficial in acute rabbit implantation. Wound-modifying behavior of the COVR implant is judged to be an important factor in preventing fibrosis. LEVEL OF EVIDENCE: NA. Laryngoscope, 128:153-159, 2018.
Authors: Ingo R Titze; Tobias Riede; Anil Palaparthi; Linda S Hynan; Amy Hamilton; Laura Toles; Ted Mau Journal: J Speech Lang Hear Res Date: 2018-12-10 Impact factor: 2.297
Authors: Yue Ma; Jennifer Long; Milan R Amin; Ryan C Branski; Edward J Damrose; Chih-Kwang Sung; Stratos Achlatis; Ann Kearney; Dinesh K Chhetri Journal: Laryngoscope Date: 2019-12-05 Impact factor: 3.325
Authors: Renee E King; Hang Kuen Lau; Haiyan Zhang; Ishnoor Sidhu; Michael B Christensen; Eric W Fowler; Linqing Li; Xinqiao Jia; Kristi L Kiick; Susan L Thibeault Journal: Regen Eng Transl Med Date: 2019-02-27
Authors: Eric K Tran; Yazeed Alhiyari; Kevin Juarez; Bhavani Shankara Gowda; Feng Schrader; Dipti P Sajed; Jennifer L Long Journal: Laryngoscope Investig Otolaryngol Date: 2022-09-26