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过表达miRNA-34a的脂肪来源干细胞移植可促进大鼠神经再生。

Transplantation of miRNA-34a overexpressing adipose-derived stem cell enhances rat nerve regeneration.

作者信息

He Xingliang, Ao Qiang, Wei Yujun, Song Jinrui

机构信息

Key Lab of School of Kinesiology, Shenyang Sport University and.

Department of Tissue Engeering, China Medical University, Shenyang, Liaoning, China.

出版信息

Wound Repair Regen. 2016 May;24(3):542-50. doi: 10.1111/wrr.12427. Epub 2016 Mar 29.

Abstract

Peripheral nerve injury is an ongoing challenge in reconstructive surgery. Adipose-derived stem cell (ADSC) application is reported to improve nerve regeneration. In the present study, we evaluated the potential benefit of 34a-ADSCs for never regeneration. Lentiviral vectors containing miRNA-34a were constructed and ADSCs were transduced. The obtained 34a-ADSCs were used to regenerate the sciatic nerve in surgically induced sciatic nerve injury rat model. Sprague-Dawley (SD) rats were randomly divided into two groups, a 34a-ADSC group and an Lv-ADSC group. Functional nerve recovery was assessed by walking track analysis at 12 weeks after surgery. In addition, histology, including light microscopy and transmission electron microscopy, and immunohistochemistry, was utilized to investigate the nerve repair effects of 34a-ADSC. Results showed that reconstruction of the injured sciatic nerve had been significantly enhanced by restoration of nerve continuity and functional recovery in the 34a-ADSC group compared with the Lv-ADSC group. Furthermore, sciatic nerve conduction velocity and compound nerve action potential in the 34a-ADSC group was much higher than that in the Lv-ADSC group (30.72 ± 2.95 m/s vs. 22.73 ± 1.91 m/s, p< 0.0001; 11.93 ± 0.76 mV vs. 9.52 ± 0.53 mV, p = 0.0418). This study raises the possibility of using miRNA-34a overexpressed ADSCs as a promising alternative for nerve regeneration.

摘要

周围神经损伤是重建手术中一直面临的挑战。据报道,应用脂肪来源干细胞(ADSC)可促进神经再生。在本研究中,我们评估了miRNA - 34a修饰的ADSCs(34a - ADSCs)对神经再生的潜在益处。构建了包含miRNA - 34a的慢病毒载体并转导ADSCs。将获得的34a - ADSCs用于手术诱导的坐骨神经损伤大鼠模型中坐骨神经的再生。将Sprague - Dawley(SD)大鼠随机分为两组,即34a - ADSC组和慢病毒转导ADSC(Lv - ADSC)组。术后12周通过行走轨迹分析评估神经功能恢复情况。此外,利用组织学方法,包括光学显微镜和透射电子显微镜检查,以及免疫组织化学方法,来研究34a - ADSC对神经修复的作用。结果显示,与Lv - ADSC组相比,34a - ADSC组神经连续性的恢复和功能的改善显著增强了受损坐骨神经的重建。此外,34a - ADSC组的坐骨神经传导速度和复合神经动作电位远高于Lv - ADSC组(30.72 ± 2.95 m/s对22.73 ± 1.91 m/s,p < 0.0001;11.93 ± 0.76 mV对9.52 ± 0.53 mV,p = 0.0418)。本研究提出了使用过表达miRNA - 34a的ADSCs作为神经再生的一种有前景的替代方法的可能性。

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