Extracellular Vesicles as a Cell-free Therapy for Cardiac Repair: a Systematic Review and Meta-analysis of Randomized Controlled Preclinical Trials in Animal Myocardial Infarction Models

Caron, Christophe; Mahmoud, Ibtisam; Derish, Ida; Schwertani, Adel; Khan, Kashif

doi:10.1007/s12015-021-10289-6

Cited by 19 publications

(6 citation statements)

References 91 publications

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“…The SECRET-HF trial has been developed on the basis of three major observations in animal models: (1) the cellular secretome, which contains soluble factors and EV, can duplicate the effects of their parental cells, an observation now made across a wide variety of preclinical disease models 10 ; (2) the best outcomes seem to come from EV derived from immature cells phenotypically close to those of the tissue to repair, 11 hence our choice of CPC as the EV donors; (3) this secretome still retains its cardio-reparative properties when given intravenously, 5 thereby enabling convenient repeated administrations.…”

Section: Discussionmentioning

confidence: 99%

First-in-man use of a cardiovascular cell-derived secretome in heart failure. Case report

Menasché,

Renault,

Hagège

et al. 2024

eBioMedicine

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Section: Discussionmentioning

confidence: 99%

First-in-man use of a cardiovascular cell-derived secretome in heart failure. Case report

Menasché,

Renault,

Hagège

et al. 2024

eBioMedicine

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“…Through the pioneering pediatric cardiac surgery in 1938 and the introduction of open-heart surgery on cardiopulmonary bypass in the 1950s mortality rates caused by congenital heart disease significantly decreased [1]. Worldwide, ischemia injury-related cardiovascular disease continues to be the primary cause of death.…”

Section: Introductionmentioning

confidence: 99%

“…Adult stem cells (ASC) have been suggested as a treatment for the infarcted heart for more than 20 years and ASC therapy for the heart has attracted a lot of attention in the clinical and basic scientific fields over the past decade [1]. The bulk of animal research and early human investigations using ASCs including Hematopoietic stem cells (HSCs), endothelial progenitor cells (EPCs), mesenchymal stem cells (MSCs), BM-derived mononuclear cells (BM-MNCs), and Cardiac stem/progenitor cells (CPC) therapy after Acute MI have shown an improvement in heart function.…”

Section: Introductionmentioning

confidence: 99%

Role of Extracellular Vesicles in Cardiac Regeneration

Verda Bitirim

2024

Extracellular Vesicles - Applications and Therapeutic Potential

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Heart failure remains a leading cause of morbidity and mortality worldwide. Despite advances in medical management and device-based therapies, there is no cure for the damaged heart. The traditional therapeutic options for patients with heart failure, such as drugs, surgeries, and transplantation, have limitations and risks, leading to the need for innovative novel therapies. Clinical and preclinical studies have shown that extracellular vesicles (EVs) secreted by transplanted cells are more effective than direct stem cell transfer in the mechanisms involved in cardiac regeneration following ischemia. EVs have gained increasing attention as potential mediators of cardiac repair and regeneration. Preclinical studies have demonstrated the regenerative effect of EVs from a variety of cardiac cell types, including cardiac progenitor cells, mesenchymal stem cells, and iPS cells. Upon EV administration, the functional capacity of the heart improved, myocardial hypertrophy reduced, and necrosis resulted in a lesser degree. This indicates that EVs’ ability to transport proteins, lipids, non-coding RNAs, and other biologically active factors plays a vital role in promoting cardiac restoration. At present, several clinical trials are exploring the therapeutic potential of EVs in heart regeneration approaches.

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“…Moreover, transplantation of C-MSC-derived EVs increased cardiomyocyte proliferation and enhanced cardiac angiogenesis in a mouse model of myocardial infarction (MI) [ 3 ]. A recent meta-analysis of pre-clinical animal studies using stem cell-derived EVs suggested that they are effective at eliciting cardiac repair post-MI [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

Electrical Stimulation Increases the Secretion of Cardioprotective Extracellular Vesicles from Cardiac Mesenchymal Stem Cells

Zhang

Shen

Kim

et al. 2023

Cells

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Clinical trials have shown that electric stimulation (ELSM) using either cardiac resynchronization therapy (CRT) or cardiac contractility modulation (CCM) approaches is an effective treatment for patients with moderate to severe heart failure, but the mechanisms are incompletely understood. Extracellular vesicles (EV) produced by cardiac mesenchymal stem cells (C-MSC) have been reported to be cardioprotective through cell-to-cell communication. In this study, we investigated the effects of ELSM stimulation on EV secretion from C-MSCs (C-MSCELSM). We observed enhanced EV-dependent cardioprotection conferred by conditioned medium (CM) from C-MSCELSM compared to that from non-stimulated control C-MSC (C-MSCCtrl). To investigate the mechanisms of ELSM-stimulated EV secretion, we examined the protein levels of neutral sphingomyelinase 2 (nSMase2), a key enzyme of the endosomal sorting complex required for EV biosynthesis. We detected a time-dependent increase in nSMase2 protein levels in C-MSCELSM compared to C-MSCCtrl. Knockdown of nSMase2 in C-MSC by siRNA significantly reduced EV secretion in C-MSCELSM and attenuated the cardioprotective effect of CM from C-MSCELSM in HL-1 cells. Taken together, our results suggest that ELSM-mediated increases in EV secretion from C-MSC enhance the cardioprotective effects of C-MSC through an EV-dependent mechanism involving nSMase2.

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Extracellular Vesicles as a Cell-free Therapy for Cardiac Repair: a Systematic Review and Meta-analysis of Randomized Controlled Preclinical Trials in Animal Myocardial Infarction Models

Cited by 19 publications

References 91 publications

First-in-man use of a cardiovascular cell-derived secretome in heart failure. Case report

First-in-man use of a cardiovascular cell-derived secretome in heart failure. Case report

Role of Extracellular Vesicles in Cardiac Regeneration

Electrical Stimulation Increases the Secretion of Cardioprotective Extracellular Vesicles from Cardiac Mesenchymal Stem Cells

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