Optimization of Autologous Muscle Stem Cell Survival in the Denervated Hemilarynx
Optimization of Autologous Muscle Stem Cell Survival in the Denervated Hemilarynx
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DOI：
10.1097/mlg.0b013e31816c438e
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发表时间：
2008-07-01
期刊：
影响因子：
2.6
通讯作者：
Clapp, D. Wade
中科院分区：
文献类型：
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作者：
Halum, Stacey L.;Hiatt, Kelly K.;Clapp, D. Wade
目的：目前声带麻痹的治疗方法不理想，不能恢复声带的动态功能。自体肌肉干细胞（MSC）治疗是一种有前途的潜在治疗声带麻痹的方法，因为它可以减轻去神经诱导的肌肉萎缩，并提供一种载体的神经营养因子，从而有可能选择性地引导神经再支配。本项目的目的是表征注射自体MSC生存在甲杓状软骨（TA）肌肉后，局部给药的辅助factors.Study设计：Animal experiments.Methods：单侧喉返神经（RLN）横断和胸锁乳突肌（类似于1克）活检的最佳条件进行了20只雄性Wistar大鼠。一个月后，将10（6）个通过逆转录病毒增强的绿色荧光蛋白（EGFP）转导标记的自体MSC注射到每只动物的去神经支配的半喉中，并使用四种辅助疗法之一：心脏毒素[（CTX）10（-5）M]、胰岛素样生长因子-1 [（IGF- 1）100 μ g/mL]、睫状神经营养因子[（CNTF）50 μ g/mL]或盐水。动物安乐死1个月后，喉收获，切片，并分析MSC survival.Results：所有标本表现出广泛的MSC生存，融合的MSC与失神经肌纤维。根据喉标本的平均荧光强度，IGF-1和CNTF对MSC存活有最大的积极影响。肌纤维直径证明肌纤维萎缩与MSC生存呈负相关，最大的MSC survival.Conclusions：AutoblastMSC治疗可能是一个未来的治疗声带麻痹的组中萎缩最少。这些发现支持了一种模型，即通过基因工程改造以分泌CNTF和/或IGF-1的MSC不仅可以促进神经再生，而且可以以自分泌的方式增强MSC的存活。
Objective: Current treatments for vocal fold paralysis are suboptimal in that they fail to restore dynamic function. Autologous muscle stem cell (MSC) therapy is a promising potential therapy for vocal fold paralysis in that it can attenuate denervation-induced muscle atrophy and provide a vehicle for delivery of neurotrophic factors, thereby potentially selectively guiding reinnervation. The goal of this project was to characterize optimal conditions for injected autologous MSC survival in the thyroarytenoid (TA) muscle following recurrent laryngeal nerve (RLN) injury by local administration of adjuvant factors.Study Design: Animal experiment.Methods: Unilateral RLN transection and sternocleidomastoid muscle (similar to 1 g) biopsies were performed in 20 male Wistar rats. One month later, 10(6) autologous MSCs labeled via retroviral-enhanced green fluorescent protein (EGFP) transduction were injected into the denervated hemilarynx of each animal with one of four adjuvant therapies: cardiotoxin [(CTX) 10(-5) M], insulin-like growth factor-1 [(IGF- 1) 100 mu g/mL], ciliary neurotrophic factor [(CNTF) 50 mu g/mL], or saline. Animals were euthanized 1 month later and larynges harvested, sectioned, and analyzed for MSC survival.Results: All specimens demonstrate extensive MSC survival, with fusion of the MSCs with the denervated myofibers. Based on mean fluorescent intensity of the laryngeal specimens, IGF-1 and CNTF had the greatest positive influence on MSC survival. Myofiber diameters demonstrated myofiber atrophy to be inversely related to MSC survival, with the least atrophy in the groups having the greatest MSC survival.Conclusions: Autologous MSC therapy may be a future treatment for vocal fold paralysis. These findings support a model whereby MSCs genetically engineered to secrete CNTF and/or IGF-1 may not only promote neural regeneration, but also enhance MSC survival in an autocrine fashion.