Li Lili, Guan Qifan, Dai Shuling, Wei Wen, Zhang Yao
Department of Cardiology, The Second Affiliated Hospital, Harbin Medical University Harbin, China.
Department of Cardiology, Yunnan Fuwai Cardiovascular Disease Hospital Kunming City, China.
Front Pharmacol. 2017 Mar 17;8:135. doi: 10.3389/fphar.2017.00135. eCollection 2017.
Bone mesenchymal stem cells (BMSCs) transplantation is a promising therapeutic approach for myocardial infarction (MI), but its application is limited by poor viability of BMSCs. In this study, we aimed to improve the survival of BMSCs by lentivirus vector mediated overexpression of integrin β1. study showed that integrin β1 overexpression could facilitate the proliferation of BMSCs under oxygen glucose deprivation condition and regulated the expression of Caspase-3, Bax, Bcl-2, FAK, and ILK in BMSCs. Next, MI was induced in rat model and Igtb1BMSCs, NullBMSCs, or NatBMSCs were transplanted by intramyocardial injection. One week later, the survival of BMSCs was higher in Itgb1 BMSCs group than in other groups. Four weeks after transplantation, heart function was significantly improved in Igtb1BMSCs group compared to other groups. The expression levels of Caspase-3 and Bax were decreased while the expression levels of Bcl-2, FAK, ILK, and VEGF were increased in the cardiomyocytes of Igtb1BMSCs group compared to other groups. In conclusion, integrin β1 overexpression could increase the survival of BMSCs and improve the efficacy of transplanted BMSCs for MI treatment. The beneficial effects may be mediated by inhibiting the apoptosis of both transplanted BMSCs and cardiomyocytes through adhesion-mediated cell survival signaling.
骨髓间充质干细胞(BMSCs)移植是一种很有前景的心肌梗死(MI)治疗方法,但其应用受到BMSCs活力低下的限制。在本研究中,我们旨在通过慢病毒载体介导整合素β1的过表达来提高BMSCs的存活率。研究表明,整合素β1的过表达可促进BMSCs在氧糖剥夺条件下的增殖,并调节BMSCs中Caspase-3、Bax、Bcl-2、FAK和ILK的表达。接下来,在大鼠模型中诱导MI,并通过心肌内注射移植Igtb1BMSCs、NullBMSCs或NatBMSCs。一周后,Igtb1 BMSCs组中BMSCs的存活率高于其他组。移植后四周,与其他组相比,Igtb1BMSCs组的心脏功能显著改善。与其他组相比,Igtb1BMSCs组心肌细胞中Caspase-3和Bax的表达水平降低,而Bcl-2、FAK、ILK和VEGF的表达水平升高。总之,整合素β1的过表达可提高BMSCs的存活率,并提高移植BMSCs治疗MI的疗效。这些有益作用可能是通过粘附介导的细胞存活信号抑制移植的BMSCs和心肌细胞的凋亡来介导的。