Stem cells and extracellular vesicles: biological regulators of physiology and disease

Abstract

Many different subpopulations of subcellular extracellular vesicles (EVs) have been described. EVs are released from all cell types and have been shown to regulate normal physiological homeostasis, as well as pathological states by influencing cell proliferation, differentiation, organ homing, injury and recovery, as well as disease progression. In this review, we focus on the bidirectional actions of vesicles from normal and diseased cells on normal or leukemic target cells; and on the leukemic microenvironment as a whole. EVs from human bone marrow mesenchymal stem cells (MSC) can have a healing effect, reversing the malignant phenotype in prostate and colorectal cancer, as well as mitigating radiation damage to marrow. The role of EVs in leukemia and their bimodal cross talk with the encompassing microenvironment remains to be fully characterized. This may provide insight for clinical advances via the application of EVs as potential therapy and the employment of statistical and machine learning models to capture the pleiotropic effects EVs endow to a dynamic microenvironment, possibly allowing for precise therapeutic intervention.

Immunomodulatory and Regenerative Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Renal Diseases

“…These therapeutic mechanisms are mediated through many biological processes, including anti-apoptosis, anti-inflammation, angiogenesis, and antifibrosis. Among the secretomes from MSCs, EVs have been shown to be the important mediator for renal protection in MSC therapy [2]. Accumulating evidence has revealed the specific miRNAs and proteins in MSC-derived EVs in renal diseases.…”

Extracellular Vesicles in Acute Kidney Injury and Clinical Applications

“…Co-isolating substances present in the conditioned culture medium may lead to a wrong conclusion about the therapeutic potential expected from the EVs. Moreover, the adequate effective amount, route of delivery, and biodistribution of MSC-derived EVs need to be determined more definitively [123,124]. Even so, EVs derived from MSCs provide us with several advantages such as low immunogenicity [125][126][127], high biological tolerance [128], and rapid internalization into target cells [129].…”

Stem Cell-Derived Extracellular Vesicles and Kidney Regeneration

“…In the last decade, many studies have characterized new mechanisms of cell-to-cell communication, capable of influencing the phenotype of target cells through the release of bioactive factors [14]. Among all soluble mediators of paracrine communication, EVs possess a central role in both physiological and pathological conditions [15]. EVs are membranous vesicles released by cells of prokaryotic, eukaryotic, and plants, in an evolutionarily conserved manner.…”