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

Am J Physiol Cell Physiol. 2019 Aug 1;317(2):C155-C166. doi: 10.1152/ajpcell.00017.2019. Epub 2019 Mar 27.

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.

Keywords: biomarkers; extracellular vesicles; leukemia; machine learning; stem cells.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism*
  • Cell Communication
  • Drug Resistance, Neoplasm
  • Extracellular Vesicles / drug effects
  • Extracellular Vesicles / genetics
  • Extracellular Vesicles / metabolism*
  • Extracellular Vesicles / pathology
  • Humans
  • Leukemia / drug therapy
  • Leukemia / genetics
  • Leukemia / metabolism*
  • Leukemia / pathology
  • Machine Learning
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism*
  • Mesenchymal Stem Cells / pathology
  • Neoplastic Stem Cells / drug effects
  • Neoplastic Stem Cells / metabolism*
  • Neoplastic Stem Cells / pathology
  • Phenotype
  • Signal Transduction
  • Systems Biology / methods
  • Tumor Microenvironment*

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor