Masgutov Ruslan, Masgutova Galina, Mukhametova Liliya, Garanina Ekaterina, Arkhipova Svetlana S, Zakirova Elena, Mukhamedshina Yana O, Margarita Zhuravleva, Gilazieva Zarema, Syromiatnikova Valeriia, Mullakhmetova Adelya, Kadyrova Gulnaz, Nigmetzyanova Mariya, Mikhail Sergeev, Igor Pankov, Yagudin Ramil, Rizvanov Albert
OpenLab "Gene and Cell Technologies", Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
Republican Clinical Hospital, Kazan, Russia.
Front Pharmacol. 2018 Mar 6;9:86. doi: 10.3389/fphar.2018.00086. eCollection 2018.
We examined the effect of transplantation of allogenic adipose-derived stem cells (ADSCs) with properties of mesenchymal stem cells (MSCs) on posttraumatic sciatic nerve regeneration in rats. We suggested an approach to rat sciatic nerve reconstruction using the nerve from the other leg as a graft. The comparison was that of a critical 10 mm nerve defect repaired by means of autologous nerve grafting versus an identical lesion on the contralateral side. In this experimental model, the same animal acts simultaneously as a test model, and control. Regeneration of the left nerve was enhanced by the use of ADSCs, whereas the right nerve healed under natural conditions. Thus the effects of individual differences were excluded and a result closer to clinical practice obtained. We observed significant destructive changes in the sciatic nerve tissue after surgery which resulted in the formation of combined contractures in knee and ankle joints of both limbs and neurotrophic ulcers only on the right limb. The stimulation of regeneration by ADSCs increased the survival of spinal L5 ganglia neurons by 26.4%, improved sciatic nerve vascularization by 35.68% and increased the number of myelin fibers in the distal nerve by 41.87%. Moreover, we have demonstrated that S100, PMP2, and PMP22 gene expression levels are suppressed in response to trauma as compared to intact animals. We have shown that ADSC-based therapy contributes to significant improvement in the regeneration.
我们研究了具有间充质干细胞(MSC)特性的同种异体脂肪来源干细胞(ADSC)移植对大鼠创伤后坐骨神经再生的影响。我们提出了一种使用另一条腿的神经作为移植物来重建大鼠坐骨神经的方法。比较的是通过自体神经移植修复的10毫米关键神经缺损与对侧相同损伤的情况。在这个实验模型中,同一只动物同时作为测试模型和对照。使用ADSC可增强左侧神经的再生,而右侧神经在自然条件下愈合。因此,排除了个体差异的影响,获得了更接近临床实践的结果。我们观察到手术后坐骨神经组织出现明显的破坏性变化,导致双下肢膝关节和踝关节形成联合挛缩,且仅右侧肢体出现神经营养性溃疡。ADSC对再生的刺激使脊髓L5神经节神经元的存活率提高了26.4%,坐骨神经血管化改善了35.68%,远端神经中髓鞘纤维数量增加了41.87%。此外,我们还证明,与完整动物相比,创伤后S100、PMP2和PMP22基因表达水平受到抑制。我们已经表明,基于ADSC的治疗有助于显著改善再生。