中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (3): 652-656.doi: 10.4103/1673-5374.346464

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

纤维蛋白神经导管复合低氧预处理脂肪源性干/祖细胞促进坐骨神经自体移植后再生

  

  • 出版日期:2023-03-15 发布日期:2022-08-28
  • 基金资助:
    这项工作得到了路德维希-马克西米利安大学医学系的支持

Hypoxic pre-conditioned adipose-derived stem/progenitor cells embedded in fibrin conduits promote peripheral nerve regeneration in a sciatic nerve graft model

Julius M. Mayer1, 2, *, #, Christian Krug1, #, Maximilian M. Saller2, Annette Feuchtinger3, Riccardo E. Giunta4, Elias Volkmer2, 5, &, Thomas Holzbach1, &   

  1. 1Department of Hand- and Plastic Surgery, Spital Thurgau, Frauenfeld, Switzerland; 2Musculoskeletal University Center Munich (MUM), Department of Orthopedics and Trauma Surgery, Ludwig-Maximilians-University (LMU), Planegg-Martinsried, Germany; 3Research Unit Analytical Pathology, Munich, Helmholtz Zentrum München – German Research Center for Environmental Health (GmbH), Neuherberg, Germany; 4Division of Hand-, Plastic- and Aesthetic Surgery, Ludwig-Maximilians-University (LMU), Munich, Germany; 5Division of Hand Surgery, Helios Klinikum München West, Munich, Germany
  • Online:2023-03-15 Published:2022-08-28
  • Contact: Julius M. Mayer, MD, julius.m.mayer@gmail.com.
  • Supported by:
    This work was support by the Faculty of Medicine, Ludwig-Maximilians-University (FöFoLe, Project 843 and 955, to TH and MMS).

摘要:

已有研究显示,脂肪源性干/祖细胞(ADSPCs)对周围神经恢复有支持作用,且低氧培养可增强脂肪源性干/祖细胞的促进神经再生能力。实验对比了纤维蛋白神经导管复合低氧预处理(2%氧气处理72h)的自体脂肪源性干/祖细胞与纤维蛋白神经导管复合常氧条件培养的自体脂肪源性干/祖细胞及无细胞神经导管对大鼠周围神经20mm缺损自体神经移植修复后的作用,并与临床金标准自体神经移植进行比较。发现相较于其他3组,缺氧预处理组的坐骨神经功能指数和静止坐骨神经指数和轴突密度明显更高,轴突的生长/分支更多,再髓鞘化更明显,而相对结缔组织面积则减少。说明纤维蛋白神经导管复合低氧预处理脂肪源性干/祖细胞是提高自体神经移植效果的一种潜在辅助手段。

https://orcid.org/0000-0002-9379-7869 (Julius M. Mayer)

Abstract: Recent results emphasize the supportive effects of adipose-derived multipotent stem/progenitor cells (ADSPCs) in peripheral nerve recovery. Cultivation under hypoxia is considered to enhance the release of the regenerative potential of ADSPCs. This study aimed to examine whether peripheral nerve regeneration in a rat model of autologous sciatic nerve graft benefits from an additional custom-made fibrin conduit seeded with hypoxic pre-conditioned (2% oxygen for 72 hours) autologous ADSPCs (n = 9). This treatment mode was compared with three others: fibrin conduit seeded with ADSPCs cultivated under normoxic conditions (n = 9); non-cell-carrying conduit (n = 9); and nerve autograft only (n = 9). A 16-week follow-up included functional testing (sciatic functional index and static sciatic index) as well as postmortem muscle mass analyses and morphometric nerve evaluations (histology, g-ratio, axon density, and diameter). At 8 weeks, the hypoxic pre-conditioned group achieved significantly higher sciatic functional index/static sciatic index scores than the other three groups, indicating faster functional regeneration. Furthermore, histologic evaluation showed significantly increased axon outgrowth/branching, axon density, remyelination, and a reduced relative connective tissue area. Hypoxic pre-conditioned ADSPCs seeded in fibrin conduits are a promising adjunct to current nerve autografts. Further studies are needed to understand the underlying cellular mechanism and to investigate a potential application in clinical practice.

Key words: adipose-derived progenitor cells, adipose-derived multipotent stem/progenitor cell, autologous nerve graft, fibrin conduit, hypoxia, hypoxic pre-conditioning, nerve defect, nerve tissue engineering, peripheral nerve regeneration, regenerative medicine