Mesenchymal stem cells transfer mitochondria into cerebral microvasculature and promote recovery from ischemic stroke

Microvasc Res. 2019 May:123:74-80. doi: 10.1016/j.mvr.2019.01.001. Epub 2019 Jan 3.

Abstract

Mesenchymal stem cells can be used as a novel treatment of ischemic stroke, but their therapeutic effect and mechanism of action require further evaluation. Mitochondrial dysfunction has core functions in ischemia-reperfusion stroke injury. Our recent research has demonstrated that mesenchymal stem cells can transfer their functional mitochondria to injured endothelial cells via tunneling nanotubes in vitro, resulting in the rescue of aerobic respiration and protection of endothelial cells from apoptosis. Therefore, we presume that the mechanisms of mitochondrial protection may be involved in stem cell-mediated rescue of injured cerebral microvasculature and recovery from ischemic stroke. In this study, the middle cerebral artery occlusion and reperfusion surgery were conducted on rats, and mesenchymal stem cells were then engrafted into the injured cerebrovascular system. Our results showed that the host cells of injured cerebral microvasculature accepted the mitochondria transferred from the transplanted stem cells, thereby resulting in significantly improving in mitochondrial activity of injured microvasculature, enhancing angiogenesis, reducing infarct volume, and improving functional recovery. Our data provided the evidence that stem cells can rescue damaged cerebrovascular system in stroke through a mechanism not yet identified.

Keywords: Endothelial cells; Ischemic stroke; Mesenchymal stem cells; Mitochondria; Tunneling nanotubes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / blood supply*
  • Brain / physiopathology
  • Cell Respiration
  • Cells, Cultured
  • Disease Models, Animal
  • Endothelial Cells / metabolism
  • Endothelial Cells / pathology*
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / physiopathology
  • Infarction, Middle Cerebral Artery / surgery*
  • Mesenchymal Stem Cell Transplantation*
  • Mesenchymal Stem Cells* / metabolism
  • Microvessels / metabolism
  • Microvessels / pathology*
  • Mitochondria / metabolism
  • Mitochondria / transplantation*
  • Motor Activity
  • Neovascularization, Physiologic
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology
  • Reperfusion Injury / surgery*
  • Time Factors