Abstract
Background: Translational studies showed positive results of stem cell therapy against myocardial infarction (MI)-induced cardiac dysfunction. Programmed death ligand 1 (PD-L1) is a key immune receptor, which modulates immune system and maintain the stability of coronary plaques. Akt is one of the signaling that exert its cardioprotective effect through regulating PD-L1. In the present study, we overexpressed PD-L1 and Akt in adipose-derived mesenchymal stem cells (AdMSC) and determined the protection against MI. Methods and Results: Adult Wistar rats were randomly separated into four groups: sham, MI, treatment of AdMSC or AdMSC overexpressed with PD-L1 and Akt (AdMSC-PDL1-Akt) immediately after MI. MI was induced by LAD ligation and ADMSC were injected into the heart around the area at risk. After 4 weeks, rats were examined by echocardiography, pressure-volume analysis, infarct size measurement, and immunohistochemistry to evaluate the efficacy of the ADMSCs on myocardium. Results demonstrated AdMSC-PDL1-Akt was more resistant to ROS in vitro , and could restore MI-induced contractile dysfunction in vivo by increasing ESPVR (P=0.048) and PRSW (P=0.015). AdMSC-PDL1-Akt could also protect hearts from MI-increased infarct size (P=0.002). Immunohistochemistry staining with caspase 3 and NFκB were upregulated in MI hearts and significantly reversed in AdMSC-PDL1-Akt group (P<0.001 and P=0.036). To clarify mechanisms underlying the effect of AdMSC-PDL1-Akt, we found it could induce normal T cells into CD25 + regulatory T cells in vitro , which is in parallel with the data shown in our in vivo immunohistochemistry study that CD25 was upregulated in AdMSC-PDL1-Akt tissues (P=0.03). Conclusions: Overexpression of PD-L1 and Akt in AdMSC could increase its resistance to ROS-related apoptosis in vitro and enhance the protective effects against MI-induced cardiac dysfunction through modulation of T cells in vivo . Keywords: AdMSC; PD-L1; myocardial infarction; regulatory T cells
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
