细胞外基质
组织工程
再生(生物学)
体内
纤维化
病理
上皮
细胞生物学
生物
医学
生物医学工程
生物技术
作者
Changying Ling,Qiyao Li,Matthew E. Brown,Yo Kishimoto,Yutaka Toya,Erin E. Devine,Kyeong-Ok Choi,Kohei Nishimoto,Ian G. Norman,Tenzin Tsegyal,Jack J. Jiang,William J. Burlingham,Sundaram Gunasekaran,Lloyd M. Smith,Brian L. Frey,Nathan V. Welham
出处
期刊:Science Translational Medicine
[American Association for the Advancement of Science (AAAS)]
日期:2015-11-18
卷期号:7 (314)
被引量:62
标识
DOI:10.1126/scitranslmed.aab4014
摘要
Patients with voice impairment caused by advanced vocal fold (VF) fibrosis or tissue loss have few treatment options. A transplantable, bioengineered VF mucosa would address the individual and societal costs of voice-related communication loss. Such a tissue must be biomechanically capable of aerodynamic-to-acoustic energy transfer and high-frequency vibration and physiologically capable of maintaining a barrier against the airway lumen. We isolated primary human VF fibroblasts and epithelial cells and cocultured them under organotypic conditions. The resulting engineered mucosae showed morphologic features of native tissue, proteome-level evidence of mucosal morphogenesis and emerging extracellular matrix complexity, and rudimentary barrier function in vitro. When grafted into canine larynges ex vivo, the mucosae generated vibratory behavior and acoustic output that were indistinguishable from those of native VF tissue. When grafted into humanized mice in vivo, the mucosae survived and were well tolerated by the human adaptive immune system. This tissue engineering approach has the potential to restore voice function in patients with otherwise untreatable VF mucosal disease.
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