Exosomes Generated From iPSC-Derivatives

Abstract

Cardiovascular disease (CVD) is the leading cause of death in modern society. The adult heart innately lacks the capacity to repair and regenerate the damaged myocardium from ischemic injury. Limited understanding of cardiac tissue repair process hampers the development of effective therapeutic solutions to treat CVD such as ischemic cardiomyopathy. In recent years, rapid emergence of induced pluripotent stem cells (iPSC) and iPSC-derived cardiomyocytes (iCM) presents a valuable opportunity to replenish the functional cells to the heart. The therapeutic effects of iPSC-derived cells have been investigated in many preclinical studies. However, the underlying mechanisms of iPSC-derived cell therapy are still unclear and limited engraftment of iCMs are well known. One facet of their mechanism is the paracrine effect of the transplanted cells. Microvesicles such as exosomes secreted from the iCMs exert protective effects by transfering the endogenous molecules to salvage the injured neighboring cells by regulating apoptosis, inflammation, fibrosis and angiogenesis. In this review, we will focus on the current advances in the exosomes from iPSC-derivatives and discuss their therapeutic potential in the treatment of CVD.

Utilization of Human Induced Pluripotent Stem Cells for Cardiac Repair

“…As patient-specific iPSCs are derived from patients themselves, they possess extensive self-renewal and differentiation potential. Despite encouraging advances in iPSCs technology, challenges remain in administration of iPSCs in the preclinic studies, including low rate of engraftment and the potential risk of tumorigenesis, which still impede clinical application of iPSCs and iPSCs-based derivatives (Jung et al, 2017;Taheri et al, 2019).…”

Fluid-based assays and precision medicine of cardiovascular diseases: the ‘hope’ for Pandora’s box?

“…Remarkably, some evidence highlighted that administration of induced pluripotent stem cells (iPSC) and iPSC-derived cardiomyocytes releasing exosomes to damaged tissues may be a frontier therapy in cardiac regenerative medicine. [82][83][84] In detail, these 'nanoshuttles' may regulate gene expression of target cells by realising specific miRNAs aimed at attenuating cardiac fibrosis and stimulating angiogenesis. [82][83][84] However, even if administration of exosomes seem to be an excellent therapeutic tool for cardioprotection or regeneration of the injured myocardium, we are so far from clinical confirmations.…”

“…[82][83][84] In detail, these 'nanoshuttles' may regulate gene expression of target cells by realising specific miRNAs aimed at attenuating cardiac fibrosis and stimulating angiogenesis. [82][83][84] However, even if administration of exosomes seem to be an excellent therapeutic tool for cardioprotection or regeneration of the injured myocardium, we are so far from clinical confirmations. [82][83][84]…”

“…[82][83][84] However, even if administration of exosomes seem to be an excellent therapeutic tool for cardioprotection or regeneration of the injured myocardium, we are so far from clinical confirmations. [82][83][84]…”

Forging the Fate of Cellular Therapies for Cardiovascular Disease

“…While the paracrine hypothesis of cell delivery originally focused on secreted proteins, the list of potential mediators is expanding 9 . RNA-based mediators and exosomes are an increasingly exciting source of cellular effects 10 . As the effects of cell delivery get parsed to potent individual mediators, the development of these mediators as therapeutics will grow.…”