Mitochondrial transfer from mesenchymal stem cells improves neuronal metabolism after oxidant injury in vitro: The role of Miro1

J Cereb Blood Flow Metab. 2021 Apr;41(4):761-770. doi: 10.1177/0271678X20928147. Epub 2020 Jun 5.

Abstract

Stroke-induced cerebral ischemia is a major cause of death and disability. The disruption of blood flow results in neuronal and glial cell death leading to brain injury. Reperfusion restores oxygen to the affected tissue, but can also cause damage through an enhanced oxidative stress and inflammatory response. This study examines mitochondrial transfer from MSC to neurons and the role it plays in neuronal preservation after oxidant injury. We observed the transfer of mitochondria from MSC to mouse neurons in vitro following hydrogen peroxide exposure. The observed transfer was dependent on cell-to-cell contact and led to increased neuronal survival and improved metabolism. A number of pro-inflammatory and mitochondrial motility genes were upregulated in neurons after hydrogen peroxide exposure. This included Miro1 and TNFAIP2, linking inflammation and mitochondrial transfer to oxidant injury. Increasing Miro1 expression in MSC improved the metabolic benefit of mitochondrial transfer after neuronal oxidant injury. Decreasing Miro1 expression had the opposite effect, decreasing the metabolic benefit of MSC co-culture. MSC transfer of mitochondria to oxidant-damaged neurons may help improve neuronal preservation and functional recovery after stroke.

Keywords: Brain ischemia; Miro1; mesenchymal stem cell transplant; mitochondrial transfer; neuronal injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Survival
  • Coculture Techniques
  • Gene Knockdown Techniques
  • Hydrogen Peroxide / toxicity
  • Inflammation / genetics
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mitochondria / transplantation*
  • Neurons / metabolism*
  • Oxidants / toxicity*
  • Oxidative Stress
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / prevention & control*
  • Tumor Necrosis Factors / genetics
  • rho GTP-Binding Proteins / metabolism*

Substances

  • M-sec protein, mouse
  • Miro-1 protein, mouse
  • Oxidants
  • Tumor Necrosis Factors
  • Hydrogen Peroxide
  • rho GTP-Binding Proteins