Mukhamedshina Yana O, Akhmetzyanova Elvira R, Kostennikov Alexander A, Zakirova Elena Y, Galieva Luisa R, Garanina Ekaterina E, Rogozin Alexander A, Kiassov Andrey P, Rizvanov Albert A
OpenLab "Gene and Cell Technologies", Institute of Fundamental Medicine and Biology, Kazan Federal University, Kazan, Russia.
Department of Histology, Cytology and Embryology, Kazan State Medical University, Kazan, Russia.
Front Pharmacol. 2018 Apr 10;9:343. doi: 10.3389/fphar.2018.00343. eCollection 2018.
The use of stem and progenitor cells to restore damaged organs and tissues, in particular, the central nervous system, is currently considered a most promising therapy in regenerative medicine. At the same time, another approach aimed at stimulating regeneration with the use of stem cells encapsulated into a biopolymer matrix and capable of creating a specific microenvironment for the implanted cells similar to the natural extracellular matrix is under active development. Here, we study effects of the application of adipose-derived mesenchymal stem cells (AD-MSCs) combined with a fibrin matrix on post-traumatic reactions in the spinal cord in rats. The AD-MSC application is found to exert a positive impact on the functional and structural recovery after spinal cord injury (SCI) that has been confirmed by the results of behavioral/electrophysiological and morphometric studies demonstrating reduced area of abnormal cavities and enhanced tissue retention in the site of injury. Immunohistochemical and real-time PCR analyses provide evidence that AD-MSC application decreases the GFAP expression in the area of SCI that might indicate the reduction of astroglial activation. Our results also demonstrate that AD-MSC application contributes to marked upregulation of PDGFβR and HSPA1b mRNA expression and decrease of Iba1 expression at the site of the central canal. Thus, the application of AD-MSCs combined with fibrin matrix at the site of SCI during the subacute period can stimulate important mechanisms of nervous tissue regeneration and should be further developed for clinical applications.
利用干细胞和祖细胞来修复受损器官和组织，尤其是中枢神经系统，目前被认为是再生医学中最具前景的治疗方法。与此同时，另一种利用封装在生物聚合物基质中的干细胞来刺激再生的方法正在积极研发中，这种干细胞能够为植入细胞创造一个类似于天然细胞外基质的特定微环境。在此，我们研究脂肪来源的间充质干细胞（AD-MSCs）与纤维蛋白基质联合应用对大鼠脊髓创伤后反应的影响。研究发现，AD-MSCs的应用对脊髓损伤（SCI）后的功能和结构恢复具有积极影响，行为/电生理和形态计量学研究结果证实了这一点，这些结果表明异常空洞面积减小，损伤部位的组织保留增强。免疫组织化学和实时PCR分析表明，AD-MSCs的应用降低了SCI区域中GFAP的表达，这可能表明星形胶质细胞活化减少。我们的结果还表明，AD-MSCs的应用有助于显著上调中央管部位PDGFβR和HSPA1b mRNA的表达，并降低Iba1的表达。因此，在亚急性期将AD-MSCs与纤维蛋白基质联合应用于SCI部位可刺激神经组织再生的重要机制，应进一步开展临床应用研究。
