Objectives Exendin-4 has the strong anti-oxidant andanti-inflammatory properties. Reactive oxygen species (ROS) produced in ischaemic niche play a pivotal role in stem cells detachment from the impairedmyocardium. To improve the poor retention and survival of transplanted stemcells in infarcted myocardium, we tested the hypothesis that pretreatment of adipose-derived stem cells (ADSCs) with Exendin-4 can improve the therapeuticefficacy of ADSCs by enhancing the adhesion.
Methods H2O2 was used to mimic ROS condition in vitro . Adhesion, apoptosis and necrosis were analysed for ADSCs pretreated with or without Exendin-4 (50 nM). The adhesiveability of ADSCs to cardiomyocytes was performed too. Cardiac function, histology, immunohistochemistry were evaluatied in the SD rats myocardialinfarction model.
Results Exendin-4 could decrease the ADSCs apoptosis and necrosis. Excessive ROS in ADSCs attenuate the adhesion-related integrins expression, which were restored in Exendin-4 pretreatment group. Meanwhile, corresponding Src-Fak complex and PI3K and Akt changes revealed that Exendin-4 activates the PI3K/Akt pathway through focal adhesion complex. In vivo , Bioluminescence imaging showed that Exendin-4 could promote ADSCs retention and survival in ischaemic microenvironment. ADSCs pretreated with Exendin-4 could significantly improve the cardiac function, decrease fibrosis, enhance vascular density, promote the paracrine effect andcardiac differentiation.
Conclusions Pretreatment by Exendin-4 maybe a promising novel candidate strategy to improve the ADSC stherapy to facilitate the cardiac repair.