Improving the function of neutrophils from chronic granulomatous disease patients using mesenchymal stem cells' exosomes

Hum Immunol. 2020 Oct-Nov;81(10-11):614-624. doi: 10.1016/j.humimm.2020.05.009. Epub 2020 Sep 3.

Abstract

In chronic granulomatous disease (CGD) patients, reactive oxygen species (ROS) production by neutrophils is impaired. So, they are susceptible to infections. Studies showed that, mesenchymal stem cells (MSCs) have protective effects on the function of neutrophils and an approach that MSCs use to apply their effects, is secreting soluble factors and exosomes. So, we investigated the effects of MSC-exosomes and MSC-conditioned media (MSC-CM) on the function and apoptosis of neutrophils in CGD patients. In this study, neutrophils were isolated from healthy donors and CGD patients and then incubated with exosomes or CM that were prepared from MSCs. Then, neutrophil respiratory burst, apoptosis and phagocytosis capacity were evaluated by NBT assay, Annexin V-PI method and Giemsa staining. It was demonstrated that both MSC-exosomes and CM could improve the phagocytosis capacity and ROS production of neutrophils in CGD patients and healthy donors. In contrast to the healthy group, in CGD patients, exosomes significantly reduced the percentage of viable neutrophils. This report indicated that MSC exosomes and CM could increase the function of the neutrophils isolated from CGD patients. But decreasing the number of the living cells is one of the limitations of them. However, it is hoped that this intervention will be developed in future studies to minimize its limitations.

Keywords: Chronic Granulomatous Disease (CGD); Conditioned Media (CM); Exosomes; Mesenchymal Stem Cells; Neutrophils.

MeSH terms

  • Adolescent
  • Adult
  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Child
  • Culture Media, Conditioned / pharmacology
  • Exosomes / metabolism*
  • Female
  • Granulomatous Disease, Chronic / blood*
  • Humans
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / metabolism*
  • Neutrophils / metabolism*
  • Protective Agents / pharmacology
  • Reactive Oxygen Species / metabolism
  • Treatment Outcome

Substances

  • Culture Media, Conditioned
  • Protective Agents
  • Reactive Oxygen Species