NSC-derived exosomes enhance therapeutic effects of NSC transplantation on cerebral ischemia in mice

Elife. 2023 Apr 27:12:e84493. doi: 10.7554/eLife.84493.

Abstract

Transplantation of neural stem cells (NSCs) has been proved to promote functional rehabilitation of brain lesions including ischemic stroke. However, the therapeutic effects of NSC transplantation are limited by the low survival and differentiation rates of NSCs due to the harsh environment in the brain after ischemic stroke. Here, we employed NSCs derived from human induced pluripotent stem cells together with exosomes extracted from NSCs to treat cerebral ischemia induced by middle cerebral artery occlusion/reperfusion in mice. The results showed that NSC-derived exosomes significantly reduced the inflammatory response, alleviated oxidative stress after NSC transplantation, and facilitated NSCs differentiation in vivo. The combination of NSCs with exosomes ameliorated the injury of brain tissue including cerebral infarction, neuronal death, and glial scarring, and promoted the recovery of motor function. To explore the underlying mechanisms, we analyzed the miRNA profiles of NSC-derived exosomes and the potential downstream genes. Our study provided the rationale for the clinical application of NSC-derived exosomes as a supportive adjuvant for NSC transplantation after stroke.

Keywords: combination treatment; exosome; mouse; neural stem cell; neuroscience; stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia* / therapy
  • Cell Differentiation / physiology
  • Cerebral Infarction
  • Exosomes*
  • Humans
  • Induced Pluripotent Stem Cells*
  • Ischemic Stroke*
  • Mice

Associated data

  • GEO/GSE217074

Grants and funding

The funders had no role in study design, data collection, and interpretation, or the decision to submit the work for publication.