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负载人脐带间充质干细胞和神经生长因子的肝素化胶原支架修复喉返神经损伤的治疗潜力研究

Insights into the Therapeutic Potential of Heparinized Collagen Scaffolds Loading Human Umbilical Cord Mesenchymal Stem Cells and Nerve Growth Factor for the Repair of Recurrent Laryngeal Nerve Injury.

作者信息

Pan Yongqin, Jiao Genlong, Yang Jingge, Guo Rui, Li Jinyi, Wang Cunchuan

机构信息

1Department of General Surgery, First Affiliated Hospital of Jinan University, No. 613 West Huangpu Avenue, Guangzhou, 510630 People's Republic of China.

2Department of Orthopedics, First Affiliated Hospital of Jinan University, Guangzhou, 510630 People's Republic of China.

出版信息

Tissue Eng Regen Med. 2017 Apr 7;14(3):317-326. doi: 10.1007/s13770-017-0032-7. eCollection 2017 Jun.

Abstract

Recurrent laryngeal nerve (RLN) injury can result in unilateral or bilateral vocal cords paralysis, thereby causing a series of complications, such as hoarseness and dyspnea. However, the repair of RLN remains a great challenge in current medicine. This study aimed to develop human umbilical mesenchymal stem cells (HuMSCs) and nerve growth factor (NGF)-loaded heparinized collagen scaffolds (HuMSCs/NGF HC-scaffolds) and evaluate their potential in the repair of RLN injury. HuMSCs/NGF HC-scaffolds were prepared through incorporating HuMSCs and NGF into heparinized collagen scaffolds that were prefabricated by freeze-drying in a template. The resulting scaffolds were characterized by FTIR, SEM, porosity, degradation , NGF release and bioactivity. A rabbit RLN injury model was constructed to appraise the performance of HuMSCs/NGF HC-scaffolds for nerve injury repair. Electrophysiology, histomorphology and diagnostic proteins expression for treated nerves were checked after application of various scaffolds. The results showed that the composite scaffolds with HuMSCs and NGF were rather helpful for the repair of broken RLN. The RLN treated with HuMSCs/NGF HC-scaffolds for 8 weeks produced a relatively normal electromyogram, and the levels of calcium-binding protein S100, neurofilament and AchE pertinent to nerve were found to be close to the normal ones but higher than those resulted from other scaffolds. Taken together, HuMSCs/NGF HC-scaffolds exhibited a high score on the nerve injury repair and may be valuable for the remedy of RLN injury.

摘要

喉返神经(RLN)损伤可导致单侧或双侧声带麻痹,从而引发一系列并发症,如声音嘶哑和呼吸困难。然而,目前医学上RLN的修复仍然是一项巨大挑战。本研究旨在开发负载人脐间充质干细胞(HuMSCs)和神经生长因子(NGF)的肝素化胶原支架(HuMSCs/NGF HC支架),并评估其在修复RLN损伤方面的潜力。通过将HuMSCs和NGF掺入经冻干预制在模板中的肝素化胶原支架中制备HuMSCs/NGF HC支架。通过傅里叶变换红外光谱(FTIR)、扫描电子显微镜(SEM)、孔隙率、降解、NGF释放和生物活性对所得支架进行表征。构建兔RLN损伤模型以评估HuMSCs/NGF HC支架对神经损伤修复的性能。在应用各种支架后,检查治疗神经的电生理学、组织形态学和诊断蛋白表达。结果表明,含有HuMSCs和NGF的复合支架对断裂的RLN修复相当有帮助。用HuMSCs/NGF HC支架治疗8周的RLN产生了相对正常的肌电图,并且发现与神经相关的钙结合蛋白S100、神经丝和乙酰胆碱酯酶(AchE)水平接近正常水平,但高于其他支架处理后的水平。综上所述,HuMSCs/NGF HC支架在神经损伤修复方面表现出高分,可能对RLN损伤的治疗有价值。

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