Oxidative stress preconditioning of mouse perivascular myogenic progenitors selects a subpopulation of cells with a distinct survival advantage in vitro and in vivo

Cell Death Dis. 2018 Jan 3;9(1):1. doi: 10.1038/s41419-017-0012-9.

Abstract

Cell engraftment, survival and integration during transplantation procedures represent the crux of cell-based therapies. Thus, there have been many studies focused on improving cell viability upon implantation. We used severe oxidative stress to select for a mouse mesoangioblast subpopulation in vitro and found that this subpopulation retained self-renewal and myogenic differentiation capacities while notably enhancing cell survival, proliferation and migration relative to unselected cells. Additionally, this subpopulation of cells presented different resistance and recovery properties upon oxidative stress treatment, demonstrating select advantages over parental mesoangioblasts in our experimental analysis. Specifically, the cells were resistant to oxidative environments, demonstrating survival, continuous self-renewal and improved migration capability. The primary outcome of the selected cells was determined in in vivo experiments in which immunocompromised dystrophic mice were injected intramuscularly in the tibialis anterior with selected or non-selected mesoangioblasts. Resistant mesoangioblasts exhibited markedly enhanced survival and integration into the host skeletal muscle, accounting for a more than 70% increase in engraftment compared with that of the unselected mesoangioblast cell population and leading to remarkable muscle recovery. Thus, the positive effects of sorting on mesoangioblast cell behaviour in vitro and in vivo suggest that a selection step involving oxidative stress preconditioning may provide a novel methodology to select for resistant cells for use in regenerative tissue applications to prevent high mortality rates upon transplantation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Cycle Checkpoints / drug effects
  • Cell Differentiation
  • Cell Line
  • Cell Movement / drug effects
  • Cell Survival / drug effects
  • Hydrogen Peroxide / pharmacology*
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Mice
  • Mice, SCID
  • Muscle, Skeletal / cytology
  • Muscular Dystrophy, Animal / therapy
  • Oxidative Stress / drug effects*
  • Protein Isoforms / metabolism
  • Reactive Oxygen Species / metabolism
  • Sarcoglycans / deficiency
  • Sarcoglycans / genetics
  • Stem Cell Transplantation
  • Stem Cells / cytology
  • Stem Cells / drug effects
  • Stem Cells / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Protein Isoforms
  • Reactive Oxygen Species
  • Sarcoglycans
  • Hydrogen Peroxide
  • p38 Mitogen-Activated Protein Kinases
  • Matrix Metalloproteinase 2