中国神经再生研究(英文版) ›› 2023, Vol. 18 ›› Issue (6): 1378-1385.doi: 10.4103/1673-5374.358605

• 原著:周围神经损伤修复保护与再生 • 上一篇    下一篇

富含纤维蛋白-胶原蛋白水凝胶壳聚糖导管复合脂肪间充质干细胞修复长距离的周围神经缺损

  

  • 出版日期:2023-06-15 发布日期:2023-01-05

Chitosan conduits enriched with fibrin-collagen hydrogel with or without adipose-derived mesenchymal stem cells for the repair of 15-mm-long sciatic nerve defect

Marwa El Soury1, 2, #, Óscar Darío García-García3, 4, #, Isabella Tarulli1, Jesús Chato-Astrain3, 4, Isabelle Perroteau1, Stefano Geuna1, 2, Stefania Raimondo1, 2, *, Giovanna Gambarotta1, 2, §,  Víctor Carriel3, 4, §   

  1. 1Department of Clinical and Biological Sciences, University of Torino, Torino, Italy; 2Neuroscience Institute Cavalieri Ottolenghi, University of Torino, Torino, Italy; 3Department of Histology, Tissue Engineering Group, University of Granada, Granada, Spain; 4Instituto de Investigacion Biosanitaria, Ibs.GRANADA, Granada, Spain
  • Online:2023-06-15 Published:2023-01-05
  • Contact: Stefania Raimondo, PhD, stefania.raimondo@unito.it.
  • Supported by:
    This study was funded by the Spanish “Plan Nacional de Investigación Científica, Desarrollo e Innovación Tecnológica, Ministerio de Economía y Competitividad (Instituto de Salud Carlos III), grants Nos. FIS PI14-1343, FIS PI17-0393, and FIS PI20-0318 co-financed by the “Fondo Europeo de Desarrollo Regional ERDF-FEDER European Union”; grant No. P18-RT-5059 by “Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020), Consejería de Transformación Económica, Industria, Conocimiento y Universidades, Junta de Andalucía, España”; and grant No. A-CTS-498-UGR18 by “Programa Operativo FEDER Andalucía 2014–2020, Universidad de Granada, Junta de Andalucía, España”, co-funded by ERDF-FEDER, the European Union (all to VC).

摘要:

天然或合成的空心导管用于修复较短距离周围神经缺损方面,不能模拟自然神经再生环境,因而在移植后的神经再生方面效果不够理想。实验评估了空心壳聚糖导管、单独使用富含纤维蛋白-胶原蛋白水凝胶的导管或进一步添加脂肪间充质干细胞(ADMSC)修复15mm大鼠坐骨神经缺损后的神经再生情况。由于水凝胶在体内的一致性和结构稳定性发生了意想不到的变化,导致15周后神经再生失败。然而,早期再生阶段(7、14和28天)的评估显示,与空心导管相比,由纤维蛋白-胶原蛋白组成的水凝胶能够上调可溶性NRG1的表达,这是一种在许旺细胞转分化中起重要作用的生长因子。说明富含纤维蛋白-胶原蛋白水凝胶的壳聚糖导管复合脂肪间充质干细胞在促进周围神经再生方面更具有潜力。今后仍有必要进行研究以评估不同的后期时间点和不同的脂肪间充质干细胞浓度对周围神经再生相关基因表达的影响。

https://orcid.org/0000-0002-8907-473X (Stefania Raimondo)

Abstract: Hollow conduits of natural or synthetic origins have shown acceptable regeneration results in short nerve gap repair; however, results are still not comparable with the current gold standard technique “autografts”. Hollow conduits do not provide a successful regeneration outcome when it comes to critical nerve gap repair. Enriching the lumen of conduits with different extracellular materials and cells could provide a better biomimicry of the natural nerve regenerating environment and is expected to ameliorate the conduit performance. In this study, we evaluated nerve regeneration in vivo using hollow chitosan conduits or conduits enriched with fibrin-collagen hydrogels alone or with the further addition of adipose-derived mesenchymal stem cells in a 15 mm rat sciatic nerve transection model. Unexpected changes in the hydrogel consistency and structural stability in vivo led to a failure of nerve regeneration after 15 weeks. Nevertheless, the molecular assessment in the early regeneration phase (7, 14, and 28 days) has shown an upregulation of useful regenerative genes in hydrogel enriched conduits compared with the hollow ones. Hydrogels composed of fibrin-collagen were able to upregulate the expression of soluble NRG1, a growth factor that plays an important role in Schwann cell transdifferentiation. The further enrichment with adipose-derived mesenchymal stem cells has led to the upregulation of other important genes such as ErbB2, VEGF-A, BDNF, c-Jun, and ATF3. 

Key words: adipose-derived stem cells, chitosan conduit, fibrin and collagen hydrogel, nerve regeneration, nerve repair, neuregulin 1, peripheral nerve, sciatic nerve