Neurotrophic factor-secreting autologous muscle stem cell therapy for the treatment of laryngeal denervation injury.
Neurotrophic factor-secreting autologous muscle stem cell therapy for the treatment of laryngeal denervation injury.
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DOI：
10.1002/lary.23519
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发表时间：
2012-11
期刊：
影响因子：
2.6
通讯作者：
Hiatt, Kelly
中科院分区：
文献类型：
--
作者：
Halum, Stacey L.;McRae, Bryan;Bijangi-Vishehsaraei, Khadijeh;Hiatt, Kelly
确定是否可以选择性地促进喉返神经（RLN）损伤后的自发神经再支配，并使用神经营养因子（NF）分泌的肌肉干细胞（MSC）载体定向到某些喉肌，而长春新碱（VNC）抑制拮抗性神经再支配。涉及原代细胞培养、基因克隆/转移和动物实验的基础科学研究。（i.）MSC存活测定用于在体外测试多个单独的NF。（二）运动神经元生长试验评估了所鉴定的NF对体外颅神经X源性（CNX）运动神经元的营养作用。（三）将治疗性NF克隆到慢病毒载体中，并转导MSC以分泌NF。60只大鼠接受左侧RLN横断损伤，并在3周时接受MSC（n=24）、分泌NF的MSC（n=24）或生理盐水（n=12）注射到左侧甲杓肌复合体（TA）中; MSC组中的一半动物同时接受长春新碱（VNC）的左侧环杓后（PCA）注射，而一半动物接受生理盐水。（一）睫状体源性神经营养因子（CNTF）对培养的MSCs具有最大的存活促进作用。（二）在CN X运动神经元培养物中加入CNTF（50 ng/mL）导致神经突生长和分支增强。（三）在动物模型中，注射的MSC与失神经支配的肌纤维融合，免疫组织化学显示基于运动终板与神经接触的增强的神经再支配，并且RT-PCR证实在CNTF分泌MSC治疗组中在最长随访（4个月）时CNTF表达稳定。MSC治疗可能在喉返神经损伤后选择性地促进和指导喉神经再支配方面具有未来的作用。证据等级：NA
To determine if the spontaneous reinnervation that characteristically ensues after recurrent laryngeal nerve (RLN) injury could be selectively promoted and directed to certain laryngeal muscles with the use of neurotrophic factor (NF)-secreting muscle stem cell (MSC) vectors while antagonistic reinnervation is inhibited with vincristine (VNC). Basic science investigations involving primary cell cultures, gene cloning/transfer, and animal experiments. (i.) MSC survival assays were used to test multiple individual NFs in vitro. (ii.) Motoneuron outgrowth assays assessed the trophic effects of identified NF on cranial nerve X-derived (CNX) motoneurons in vitro. (iii.) Therapeutic NF was cloned into a lentiviral vector, and MSCs were tranduced to secrete NF. 60 rats underwent left RLN transection injury, and at 3 weeks received injections of either MSCs (n=24), MSCs secreting NF (n=24), or saline (n=12) into the left thyroarytenoid muscle complex (TA); half of the animals in the MSC groups simultaneously received left posterior cricoarytenoid (PCA) injections of vincristine (VNC) while half the animals received saline. (i.) Ciliary-derived neurotrophic factor (CNTF) had the greatest survival-promoting effect on MSCs in culture. (ii.) Addition of CNTF (50 ng/mL) to CN X motoneuron cultures resulted in enhanced neurite outgrowth and branching. (iii.) In the animal model, the injected MSCs fused with the denervated myofibers, immunohistochemistry demonstrated enhanced reinnervation based on motor endplate to nerve contact, and RT-PCR confirmed stable CNTF expression at longest follow-up (4 months) in the CNTF-secreting MSC treated groups. MSC therapy may have a future role in selectively promoting and directing laryngeal reinnervation after RLN injury. Level of evidence: NA
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影响因子：
158.5
作者：
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通讯作者：
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作者：
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