中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (9): 1529-1537.doi: 10.4103/1673-5374.215265

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

无支架组织工程化神经导管促进损伤胫神经再生和功能恢复

  

  • 收稿日期:2017-07-19 出版日期:2017-09-15 发布日期:2017-09-15
  • 基金资助:

    NIH,NIAMS,NIBIB基金项目;Barbara和Richard Raynor医学基金会项目

Scaffoldless tissue-engineered nerve conduit promotes peripheral nerve regeneration and functional recovery after tibial nerve injury in rats

Aaron M. Adams1, Keith W. VanDusen1, Tatiana Y. Kostrominova3, Jacob P. Mertens1, Lisa M. Larkin1, 2   

  1. 1 Department of Molecular and Integrated Physiology, University of Michigan, Ann Arbor, MI, USA
    2 Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
    3 Department of Anatomy and Cell Biology, Indiana University School of Medicine, Northwest, Gary, IN, USA
  • Received:2017-07-19 Online:2017-09-15 Published:2017-09-15
  • Contact: Lisa M. Larkin, Ph.D.,llarkin@umich.edu.
  • Supported by:

    This study was supported by a NIH, NIAMS, NIBIB funded grant R01 AR054778-05 and gift from the Barbara and Richard Raynor Medical Foundation Award.

摘要:

 实验比较了组织工程化神经导管(ENC)、组织工程化成纤维细胞导管(EFC)和自体神经移植修复10 mm胫神经缺损的效果。组织工程化神经导管是利用原代成纤维细胞和孕15d大鼠神经细胞制备而成,组织工程化成纤维细胞导管则仅由原代成纤维细胞制备而成。修复后12周,通过检测内侧腓肠肌收缩特性,腓肠肌外侧远端运动神经传导速度,以及肌肉和神经HE染色和免疫组化染色评估神经修复效果。自体神经移植、组织工程化神经导管,组织工程化成纤维细胞导管,可分别恢复96%,87%,84%的腓肠肌外侧远端运动神经传导速度,恢复100%,44%,44%的内侧腓肠肌力量,恢复63%,61%,67%的内侧腓肠肌质量。神经组织学检测显示,自体神经移植后胫神经再生的轴突较大;组织工程化神经导管修复的胫神经再生的轴突也较大,但数量较少;组织工程化成纤维细胞导管修复的胫神经再生的轴突较小。各种神经修复的内侧腓肠肌肌纤维横断面积相近。总之,胎鼠神经细胞对于无支架组织工程化神经导管修复周围神经缺损不是必需的,单纯组织工程化成纤维细胞导管足以用来制备用于周围神经缺损修复的组织工程化神经导管。

orcid:0000-0003-0538-1060(Lisa M. Larkin)

关键词: 神经再生, 周围神经缺损, 神经导管, 组织工程, 成纤维细胞, 神经导管

Abstract:

Damage to peripheral nerve tissue may cause loss of function in both the nerve and the targeted muscles it innervates. This study compared the repair capability of engineered nerve conduit (ENC), engineered fibroblast conduit (EFC), and autograft in a 10-mm tibial nerve gap. ENCs were fabricated utilizing primary fibroblasts and the nerve cells of rats on embryonic day 15 (E15). EFCs were fabricated utilizing primary fibroblasts only. Following a 12-week recovery, nerve repair was assessed by measuring contractile properties in the medial gastrocnemius muscle, distal motor nerve conduction velocity in the lateral gastrocnemius,and histology of muscle and nerve. The autografts, ENCs and EFCs reestablished 96%, 87% and 84% of native distal motor nerve conduction velocity in the lateral gastrocnemius, 100%, 44% and 44% of native specific force of medical gastrocnemius, and 63%, 61% and 67% of native medial gastrocnemius mass, respectively. Histology of the repaired nerve revealed large axons in the autograft, larger but fewer axons in the ENC repair, and many smaller axons in the EFC repair. Muscle histology revealed similar muscle fiber cross-sectional areas among autograft, ENC and EFC repairs. In conclusion, both ENCs and EFCs promoted nerve regeneration in a 10-mm tibial nerve gap repair, suggesting that the E15 rat nerve cells may not be necessary for nerve regeneration, and EFC alone can suffice for peripheral nerve injury repair.
 

Key words: nerve regeneration, peripheral nerve repair, neural conduit, tissue engineering, fibroblasts, neural cells