Cartarozzi Luciana P, Spejo Aline B, Ferreira Rui S, Barraviera Benedito, Duek Eliana, Carvalho Juliana L, Góes Alfredo M, Oliveira Alexandre L R
Department of Structural and Functional Biology, UNICAMP, CP 6109, CEP 13083-970 Campinas, SP, Brazil.
Department of Structural and Functional Biology, UNICAMP, CP 6109, CEP 13083-970 Campinas, SP, Brazil.
Brain Res Bull. 2015 Mar;112:14-24. doi: 10.1016/j.brainresbull.2015.01.005. Epub 2015 Jan 17.
The present study investigated the effectiveness of mesenchymal stem cells (MSCs) associated with a fibrin scaffold (FS) for the peripheral regenerative process after nerve tubulization. Adult female Lewis rats received a unilateral sciatic nerve transection followed by repair with a polycaprolactone (PCL)-based tubular prosthesis. Sixty days after injury, the regenerated nerves were studied by immunohistochemistry. Anti-p75NTR immunostaining was used to investigate the reactivity of the MSCs. Basal labeling, which was upregulated during the regenerative process, was detected in uninjured nerves and was significantly greater in the MSC-treated group. The presence of GFP-positive MSCs was detected in the nerves, indicating the long term survival of such cells. Moreover, there was co-localization between MSCs and BNDF immunoreactivity, showing a possible mechanism by which MSCs improve the reactivity of SCs. Myelinated axon counting and morphometric analyses showed that MSC engrafting led to a higher degree of fiber compaction combined with a trend of increased myelin sheath thickness, when compared with other groups. The functional result of MSC engrafting was that the animals showed higher motor function recovery at the seventh and eighth week after lesion. The findings herein show that MSC+FS therapy improves the nerve regeneration process by positively modulating the reactivity of SCs.
本研究调查了间充质干细胞(MSCs)与纤维蛋白支架(FS)联合用于神经管道化后周围神经再生过程的有效性。成年雌性Lewis大鼠接受单侧坐骨神经横断,随后用基于聚己内酯(PCL)的管状假体进行修复。损伤60天后,通过免疫组织化学研究再生神经。使用抗p75NTR免疫染色来研究MSCs的反应性。在未损伤的神经中检测到基础标记,其在再生过程中上调,并且在MSC治疗组中显著更高。在神经中检测到GFP阳性MSCs的存在,表明这些细胞的长期存活。此外,MSCs与脑源性神经营养因子(BNDF)免疫反应性之间存在共定位,显示了MSCs改善雪旺细胞(SCs)反应性的一种可能机制。有髓轴突计数和形态计量分析表明,与其他组相比,MSC植入导致更高程度的纤维压实以及髓鞘厚度增加的趋势。MSC植入的功能结果是,动物在损伤后第七和第八周表现出更高的运动功能恢复。本文的研究结果表明,MSC+FS疗法通过正向调节SCs的反应性来改善神经再生过程。