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Delivery of SAV-siRNA via Exosomes from Adipose-Derived Stem Cells for the Treatment of Myocardial Infarction

  • Original Article
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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Background:

Myocardial infarction (MI) leads to cardiomyocyte death, poor cardiac remodeling, and heart failure, making it a major cause of mortality and morbidity. To restore cardiac pumping function, induction of cardiomyocyte regeneration has become a focus of academic interest. The Hippo pathway is known to regulate cardiomyocyte proliferation and heart size, and its inactivation allows adult cardiomyocytes to re-enter the cell cycle.

Methods:

In this study, we investigated whether exosomes from adipose-derived stem cells (ADSCs) could effectively transfer siRNA for the Hippo pathway regulator Salvador (SAV) into cardiomyocytes to induce cardiomyocyte regeneration in a mouse model of MI.

Results:

Our results showed that exosomes loaded with SAV-siRNA effectively transferred siRNA into cardiomyocytes and induced cardiomyocyte re-entry into the cell cycle, while retaining the previously demonstrated therapeutic efficacy of ADSC-derived exosomes to improve post-infarction cardiac function through anti-fibrotic, pro-angiogenic, and other effects.

Conclusions:

Our findings suggest that siRNA delivery via ADSC-derived exosomes may be a promising approach for the treatment of MI.

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Data availability statement

The datasets generated and analyzed during the present study are available from the corresponding author on reasonable request.

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Authors and Affiliations

  1. Department of Cardiac Surgery, The Fifth Affiliated Hospital of Sun Yat-Sen University, No. 52, Meihua East Road, Zhuhai, Guangdong, People’s Republic of China

    Weizhe Bai, Jiebin Zuo, Yang Li & Gang Li

  2. Center for Infection and Immunity, Guangdong Provincial Key Laboratory of Biomedical Imaging, The Fifth Affiliated Hospital of Sun Yat-Sen University, No. 52, Meihua East Road, Zhuhai, Guangdong, People’s Republic of China

    Tianchuan Zhu & Xi Huang

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  1. Weizhe Bai
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  5. Xi Huang
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Contributions

WZB contributed the central idea, analysed most of the data, and wrote the initial draft of the paper. TCZ, JBZ, YL, XH and GL contributed to refining the ideas, carrying out additional analyses and finalizing this paper.

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Correspondence to Xi Huang or Gang Li.

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The authors declare that they have no conflict of interest.

Ethical Statement

All animal experiments were approved by the Animal Research Committee of the Fifth Affiliated Hospital of Sun Yat-sen University (No. 00243), in compliance with the “Guidelines for the Care and Use of Experimental Animals” of the National Institutes of Health (NIH Publication, 8th Edition, 2011). All donors were adults and signed an informed consent form.

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Bai, W., Zhu, T., Zuo, J. et al. Delivery of SAV-siRNA via Exosomes from Adipose-Derived Stem Cells for the Treatment of Myocardial Infarction. Tissue Eng Regen Med 20, 1063–1077 (2023). https://doi.org/10.1007/s13770-023-00588-z

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