Optimal electrical stimulation boosts stem cell therapy in nerve regeneration.
Optimal electrical stimulation boosts stem cell therapy in nerve regeneration.
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DOI：
10.1016/j.biomaterials.2018.07.015
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发表时间：
2018-10
期刊：
影响因子：
14
通讯作者：
Jia X
中科院分区：
文献类型：
--
作者：
Du J;Zhen G;Chen H;Zhang S;Qing L;Yang X;Lee G;Mao HQ;Jia X
在美国，每年约有36万人因周围神经损伤而不能完全康复，并导致严重的残疾。干细胞治疗在周围神经再生方面有很大的前景，但在体内维持干细胞的活性和分化潜能仍然是移植的主要障碍。利用自制的96孔垂直电刺激(ES)平台，研究了不同刺激脉冲频率、持续时间和电场方向对人神经脊干细胞(NCSC)分化的影响。我们观察了培养在20 Hz，100μS脉冲，电位梯度为200 mV/mm的阴极上的神经干细胞的树突形态，并促进了神经元的分化。我们进一步评估了一种新的以细胞为基础的疗法的效果，该疗法以优化的脉动性神经干细胞为基础，用于周围神经再生后的体内移植。对60只裸鼠造成15 mm的坐骨神经损伤，并进行手术修复。将损伤动物随机分为空白对照组、ES组、NCSC组、NCSC+ES组和自体神经移植组，每组12只。ES组和NCSC+ES组在手术修复1h后立即应用优化的ES。在术后6周或12周(每组6例)通过行为学(T台步态分析)、湿肌肉质量、组织形态计量学和免疫组织化学分析来评估康复情况。ES+NCSC组的腓肠肌湿质量与自体神经移植相近，明显高于其他组(p<；0.05)。定量组织形态计量学分析和走秀步态分析显示，ES对NCSCs有类似的改善(p<；0.05)。免疫组织化学分析显示，NCSC+ES组的雪旺细胞(SC)分化程度高于NCSC组(p<；0.05)。总体而言，神经干细胞移植的ES显著促进了损伤和修复后的神经再生，与自体移植治疗相当。因此，ES可能是调节干细胞存活和分化的生化和物理信号的有效替代。这种新的基于细胞的干预为改善周围神经修复后的结果提供了一种有效和安全的方法。
Peripheral nerve injuries often lead to incomplete recovery and contribute to significant disability to approximately 360,000 people in the USA each year. Stem cell therapy holds significant promise for peripheral nerve regeneration, but maintenance of stem cell viability and differentiation potential in vivo are still major obstacles for translation. Using a made-in-house 96-well vertical electrical stimulation (ES) platform, we investigated the effects of different stimulating pulse frequency, duration and field direction on human neural crest stem cell (NCSC) differentiation. We observed dendritic morphology with enhanced neuronal differentiation for NCSCs cultured on cathodes subject to 20 Hz, 100μs pulse at a potential gradient of 200 mV/mm. We further evaluated the effect of a novel cell-based therapy featuring optimized pulsatile ES of NCSCs for in vivo transplantation following peripheral nerve regeneration. 15 mm critical-sized sciatic nerve injuries were generated with subsequent surgical repair in sixty athymic nude rats. Injured animals were randomly assigned into five groups (N = 12 per group): blank control, ES, NCSC, NCSC + ES, and autologous nerve graft. Optimized ES was applied immediately after surgical repair for 1 h in ES and NCSC + ES groups. Recovery was assessed by behavioral (CatWalk gait analysis), wet muscle-mass, histomorphometric, and immunohistochemical analyses at either 6 or 12 weeks after surgery (N = 6 per group). Gastrocnemius muscle wet mass measurements in ES + NCSC group were comparable to autologous nerve transplantation and significantly higher than other groups (p < 0.05). Quantitative histomorphometric analysis and catwalk gait analysis showed similar improvements by ES on NCSCs (p < 0.05). A higher number of viable NCSCs was shown via immunochemical analysis, with higher Schwann cell (SC) differentiation in the NCSC + ES group compared to the NCSC group (p < 0.05). Overall, ES on NCSC transplantation significantly enhanced nerve regeneration after injury and repair, and was comparable to autograft treatment. Thus, ES can be a potent alternative to biochemical and physical cues for modulating stem cell survival and differentiation. This novel cell-based intervention presents an effective and safe approach for improved outcomes after peripheral nerve repair.
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影响因子：
3.7
作者：
Chang KA;Kim JW;Kim JA;Lee SE;Kim S;Suh WH;Kim HS;Kwon S;Kim SJ;Suh YH
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