Department of Otolaryngology-Head and Neck Surgery, Indiana University School of Medicine, Indianapolis, Indiana, U.S.A.
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana, U.S.A.
Laryngoscope. 2024 Dec;134(12):4988-4997. doi: 10.1002/lary.31642. Epub 2024 Jul 16.
Vocal fold paralysis impairs quality of life, and no curative injectable therapy exists. We evaluated injection of a novel in situ polymerizing (scaffold-forming) collagen in the presence and absence of muscle-derived motor-endplate expressing cells (MEEs) to promote medialization and recurrent laryngeal nerve (RLN) regeneration in a porcine model of unilateral vocal fold paralysis.
Twelve Yucatan minipigs underwent right RLN transection. Autologous muscle progenitor cells were isolated from muscle biopsies, differentiated, and induced to MEEs. Three weeks after RLN injury, animals received injections of collagen, collagen containing MEEs, or saline into the paralyzed right vocal fold. Stimulated laryngeal electromyography and acoustic vocalization were used for function assessments. Larynges were harvested and underwent histologic, gene expression, and further quantitative analyses.
Injections were well-tolerated, with the collagen scaffold showing immunotolerance and collagen-encapsulated MEEs remaining viable. Collagen-treated paralyzed vocal folds showed increased laryngeal adductor muscle volumes relative to that of the uninjured side, with those receiving MEEs and collagen showing the highest volumes. Muscles injected with MEEs and collagen demonstrated increased expression of select neurotrophic (BDNF and NTN1), motor-endplate (DOK7, CHRNA1, and MUSK), and myogenic (MYOG and MYOD) related genes relative to saline controls.
In a porcine model of unilateral vocal fold paralysis, injection of in situ polymerizing collagen in the absence and presence of MEEs enhanced laryngeal adductor muscle volume, modulated expression of neurotrophic and myogenic factors, and avoided adverse material-mediated immune responses. Further study is needed to determine long-term functional outcomes with this novel therapeutic approach.
NA Laryngoscope, 134:4988-4997, 2024.
声带麻痹会损害生活质量，目前尚无有效的注射治疗方法。我们评估了在存在和不存在表达肌肉源性运动终板的细胞（MEE）的情况下，注射新型原位聚合（支架形成）胶原，以促进猪单侧声带麻痹模型中的内侧化和喉返神经（RLN）再生。
12 头 Yucatan 小型猪接受右侧 RLN 切断术。从肌肉活检中分离出自体肌肉祖细胞，进行分化，并诱导形成 MEE。在 RLN 损伤后 3 周，动物接受胶原、含 MEE 的胶原或生理盐水注射到麻痹的右侧声带。使用刺激性喉肌电图和声学发声评估功能。收获喉并进行组织学、基因表达和进一步的定量分析。
注射耐受良好，胶原支架显示免疫耐受性，胶原包封的 MEE 保持活力。与未受伤侧相比，接受胶原治疗的麻痹性声带的喉内收肌体积增加，而接受 MEE 和胶原治疗的声带显示出最大的体积。注射 MEE 和胶原的肌肉显示出选择的神经营养因子（BDNF 和 NTN1）、运动终板（DOK7、CHRNA1 和 MUSK）和肌源性（MYOG 和 MYOD）相关基因的表达增加，与盐水对照组相比。
在单侧声带麻痹的猪模型中，原位聚合胶原的注射在不存在和存在 MEE 的情况下增强了喉内收肌的体积，调节了神经营养和肌源性因子的表达，并避免了不良材料介导的免疫反应。需要进一步的研究来确定这种新的治疗方法的长期功能结果。
NA 喉镜，134:4988-4997,2024.
