Abstract

Outstanding progress has been achieved in developing therapeutic options for reasonably alleviating symptoms and prolonging the lifespan of patients suffering from myocardial infarction (MI). Current treatments, however, only partially address the functional recovery of post-infarcted myocardium, which is in fact the major goal for effective primary care. In this context, we largely investigated novel cell and TE tissue engineering therapeutic approaches for cardiac repair, particularly using multipotent mesenchymal stromal cells (MSC) and natural extracellular matrices, from pre-clinical studies to clinical application. A further step in this field is offered by MSC-derived extracellular vesicles (EV), which are naturally released nanosized lipid bilayer-delimited particles with a key role in cell-to-cell communication. Herein, in this review, we further describe and discuss the rationale, outcomes and challenges of our evidence-based therapy approaches using Wharton’s jelly MSC and derived EV in post-MI management.

Highlights

  • Cardiovascular diseases remain the most common cause of mortality worldwide [1].A long list of risks including sedentary lifestyle and obesity among other key factors are known to potentially harm de cardiovascular system [2]

  • Cardiac tissue engineering (TE) emerged as a new therapeutic modality combining reparative cells with supporting materials in a three-dimensional (3D) context, their clinical application is still very limited [8]. Another strategy involving the use of extracellular vesicles (EV), which are double-layered membrane nanovesicles secreted by most cells to their microenvironment, has gained interest

  • Gene Therapy (ISCT), mesenchymal stromal cells (MSC) must show: (i) plastic-adherence under standard in vitro culture conditions; (ii) specific surface expression pattern including the presence of CD105, CD73 and CD90, and absence of CD45, CD14, CD79α and human leukocyte antigen (HLA)-DR; and (iii) in vitro ability to differentiate into mesodermal cell lineages [13]

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Summary

Background

Cardiovascular diseases remain the most common cause of mortality worldwide [1]. A long list of risks including sedentary lifestyle and obesity among other key factors are known to potentially harm de cardiovascular system [2]. Over the past few decades, this clinical scenario was spurred by initiatives addressing the design, development and assessment of a number of cell-based therapies to increase cardiac function recovery following MI [6] In this context, the first efforts using mixed or enriched bone marrow mononuclear cell populations were extremely inefficient due to low cell retention, survival, and differentiation rates once administered. Cardiac tissue engineering (TE) emerged as a new therapeutic modality combining reparative cells with supporting materials (either natural or synthetic) in a three-dimensional (3D) context, their clinical application is still very limited [8] In present times, another strategy involving the use of extracellular vesicles (EV), which are double-layered membrane nanovesicles secreted by most cells to their microenvironment, has gained interest. We review the scientific bases, current therapy toolkit and associated outcomes as well as the future challenges for the development of novel treatments using MSC-EV

Wharton’s Jelly Mesenchymal Stromal Cells
Cardiac Extracellular Matrices
Evidence-Based Pre-Clinical Outcomes
PeriCord: A Valuable CASE in Scalability and GMP Biomanufacturing of Cardiac Bioimplants
Mesenchymal Stromal Cell-Secreted Extracellular Vesicles
MSC-EV-Based Products
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