Abstract 16413: Molecular Imaging of Apelin on Enhancing Survival of Mesenchymal Stem Cells in Hindlimb Mice by Differential Regulation of Autophagy
Introduction: Stem cell therapy has exerted a promising approach against ischemic vascular diseases in past decade. Nevertheless, somatic stem cells, especially mesenchymal stem cells, can hardly long-term survive in vivo. Apelin, a novel peptide with significant cardio protective properties,has beneficial effects on vascular protection. This study was designed to evaluate the role and mechanism of apelin in the therapeutic efficacy of mesenchymal stem cells in hindlimb ischemia mice with molecular imaging method.
Methods Mesenchymal: stem cells (MSCs) expressing firefly luciferase were isolated from ß-actin-luc transgenic mice and exposed to hypoxia/reoxygenation with apelin(10-6mol/L)treatment for 24 hours.Cell survival and proliferation were assessed by bioluminescent imaging (BLI). Autophagy was evaluated by immunofluorescence and transmission electron microscope. Wild-type FVB mice underwent femoral artery ligation and received MSCs(1х106)or MSCs with apelin via intra-quadriceps femoris muscle injection. Cell survival was imaged by BLI. The expressions of LC3, p62, Akt, AMPK, mTOR and Beclin-1 in MSCs treated with apelin were analyzed by Western blot.
RESULTS: In vivo BLI revealed 80% acute donor cell death of MSCs within 3 weeks after transplantation in control group,while signals of injected cells were still present after 6 weeks in the MSCs with apelin group (P<0.05). In vitro cell study revealed that apelin could increase MSCs’ proliferation via promoting autophagy during ischemia, which was accompanied by AMPK activation and mammalian target of rapamycin (mTOR) inhibition(P<0.05). On the contrary, apelin inhibited autophagy during reoxygenation accompanied by the activation of Akt and inhibition of beclin1.
Conclusions: Apelin has beneficial effects on the survival maintenance of mesenchymal stem cells in hindlimb mice possibly through a differential regulation of autophagy through AMPK-mTOR and Akt-beclin1 signal pathways.
- © 2013 by American Heart Association, Inc.