Liu Xing-Long, Zhang Wei, Tang Sheng-Jian
Plastic Surgery Institute of Weifang Medical University Weifang, 261041, Shandong Province, China.
Int J Clin Exp Pathol. 2013 Dec 15;7(1):174-83. eCollection 2014.
Adipose tissue-derived mesenchymal stem cells (ADSCs) are of great interest as a cellular therapeutic agent for regenerative and immunomodulatory purposes. The aim of this study was to investigate whether ADSCs transplantation could promote nerve repair in rats of cerebral ischemia-reperfusion (I/R) injury. We isolated and cultured human ADSCs, and then measured cell surface antigens by flow cytometry and immunofluorescence. Healthy SD rats were randomly divided into sham group, MCAO group, MCAO+vehicle group and MCAO+ADSCs group. Cerebral ischemia-reperfusion injury was induced by middle cerebral artery occlusion (MCAO). Then the human ADSCs were transplanted into the brain of rats 24 h after MCAO. The mRNA level of BDNF (brain derived neurotrophic factor, BDNF), NGF (nerve growth factor, NGF) and bFGF (basic fibroblasts growth factor, bFGF) were detected by real-time PCR at different time points (d7, d14, d21 and d28 after MCAO). Meanwhile, the neurological deficit scores were estimated. The neurological deficit of rats in MCAO+ADSCs group attenuated at d7 in contrast to the MCAO+vehicle group (P<0.05). Subsequently, they were dramatically ameliorated with the time especially at d28. At d7, d14, d21 and d28 after ADSCs transplantation, BDNF, NGF and bFGF mRNA in MCAO+ADSCs group were strikingly higher than those in MCAO+vehicle group, and these two groups both reached the peak at d14. The western blotting results showed that BDNF and Bcl-2 expressed higher in MCAO+ADSCs group than MCAO+vehicle group. Therefore, our current results suggest that ADSCs promote nerve repair after injury through elevating the expression of neurotrophic factors and inhibiting the apoptosis of neural cells.
脂肪组织来源的间充质干细胞(ADSCs)作为一种用于再生和免疫调节目的的细胞治疗剂备受关注。本研究的目的是探讨ADSCs移植是否能促进脑缺血再灌注(I/R)损伤大鼠的神经修复。我们分离并培养了人ADSCs,然后通过流式细胞术和免疫荧光检测细胞表面抗原。将健康的SD大鼠随机分为假手术组、大脑中动脉闭塞(MCAO)组、MCAO+载体组和MCAO+ADSCs组。通过大脑中动脉闭塞(MCAO)诱导脑缺血再灌注损伤。然后在MCAO后24小时将人ADSCs移植到大鼠脑内。在不同时间点(MCAO后第7天、第14天、第21天和第28天)通过实时PCR检测脑源性神经营养因子(BDNF)、神经生长因子(NGF)和碱性成纤维细胞生长因子(bFGF)的mRNA水平。同时,评估神经功能缺损评分。与MCAO+载体组相比,MCAO+ADSCs组大鼠在第7天的神经功能缺损有所减轻(P<0.05)。随后,随着时间的推移,尤其是在第28天,神经功能缺损明显改善。在ADSCs移植后的第7天、第14天第21天和第28天,MCAO+ADSCs组中BDNF、NGF和bFGF的mRNA显著高于MCAO+载体组,且两组均在第14天达到峰值。蛋白质印迹结果显示,MCAO+ADSCs组中BDNF和Bcl-2的表达高于MCAO+载体组。因此,我们目前的结果表明,ADSCs通过提高神经营养因子的表达和抑制神经细胞凋亡来促进损伤后的神经修复。