The Stem Cell Adjuvant with Exendin-4 Repairs the Heart After Myocardial Infarction Via STAT3 Activation

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2014 May 1

PMID 24779911

Citations 13

Authors

Jianfeng Liu

Haibin Wang

Yan Wang

Yujing Yin

Zhiyan Du

Zhiqiang Liu

Junjie Yang

Shunying Hu

Changyong Wang

Yundai Chen

Affiliations

Soon will be listed here.

Abstract

The poor survival of cells in ischaemic myocardium is a major obstacle for stem cell therapy. Exendin-4 holds the potential of cardioprotective effect based on its pleiotropic activity. This study investigated whether Exendin-4 in conjunction with adipose-derived stem cells (ADSCs) could improve the stem cell survival and contribute to myocardial repairs after infarction. Myocardial infarction (MI) was induced by the left anterior descending artery ligation in adult male Sprague-Dawley rats. ADSCs carrying double-fusion reporter gene [firefly luciferase and monomeric red fluorescent protein (fluc-mRFP)] were quickly injected into border zone of MI in rats treated with or without Exendin-4. Exendin-4 enhanced the survival of transplanted ADSCs, as demonstrated by the longitudinal in vivo bioluminescence imaging. Moreover, ADSCs adjuvant with Exendin-4 decreased oxidative stress, apoptosis and fibrosis. They also improved myocardial viability and cardiac function and increased the differentiation rates of ADSCs into cardiomyocytes and vascular smooth muscle cells in vivo. Then, ADSCs were exposed to hydrogen peroxide/serum deprivation (H(2)O(2)/SD) to mimic the ischaemic environment in vitro. Results showed that Exendin-4 decreased the apoptosis and enhanced the paracrine effect of ADSCs. In addition, Exendin-4 activated signal transducers and activators of transcription 3 (STAT3) through the phosphorylation of Akt and ERK1/2. Furthermore, Exendin-4 increased the anti-apoptotic protein Bcl-2, but decreased the pro-apoptotic protein Bax of ADSCs. In conclusion, Exendin-4 could improve the survival and therapeutic efficacy of transplanted ADSCs through STAT3 activation via the phosphorylation of Akt and ERK1/2. This study suggests the potential application of Exendin-4 for stem cell-based heart regeneration.

Citing Articles

Immunomodulatory and Antioxidative potentials of adipose-derived Mesenchymal stem cells isolated from breast versus abdominal tissue: a comparative study.

Abu-Shahba N, Mahmoud M, Abdel-Rasheed M, Darwish Y, AbdelKhaliq A, Mohammed E Cell Regen. 2020; 9(1):18.

PMID: 33020894 PMC: 7536259. DOI: 10.1186/s13619-020-00056-2.

Analyzing Impetus of Regenerative Cellular Therapeutics in Myocardial Infarction.

Chang M, Chiu Y, Li J, Cheah K, Lin H J Clin Med. 2020; 9(5).

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Targeting Altered Mitochondrial Biogenesis in the Brain of Diabetic Rats: Potential Effect of Pioglitazone and Exendin-4.

Mostafa Tork O, Rashed L, Sadek N, Abdel-Tawab M Rep Biochem Mol Biol. 2020; 8(3):287-300.

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Protective Effect Of Vasicine Against Myocardial Infarction In Rats Via Modulation Of Oxidative Stress, Inflammation, And The PI3K/Akt Pathway.

Jiang T, Zhang L, Ding M, Li M Drug Des Devel Ther. 2019; 13:3773-3784.

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Activation of cannabinoid receptor type II by AM1241 protects adipose-derived mesenchymal stem cells from oxidative damage and enhances their therapeutic efficacy in myocardial infarction mice Stat3 activation.

Han D, Li X, Fan W, Chen J, Gou T, Su T Oncotarget. 2017; 8(39):64853-64866.

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