Exosomes Treatment Mitigates Ischemic Brain Damage but Does Not Improve Post-Stroke Neurological Outcome

Cell Physiol Biochem. 2019;52(6):1280-1291. doi: 10.33594/000000090.

Abstract

Background/aims: Recent studies demonstrated that the treatment with mesenchymal stem cells (MSCs) obtained from the human umbilical cord blood improved survival, reduced brain damage, prevented apoptosis, suppressed inflammatory responses, downregulated the DNA damage-inducing genes, upregulated the DNA repair genes, and facilitated neurological recovery in stroke-induced animals. Emerging stroke literature supports the concept that the exosomes released from MSCs are the primary biological principles underlying the post-stroke neuroprotection offered by MSCs treatment.

Methods: Because the treatment with exosomes has a great potential to overcome the limitations associated with cell-based therapies, we tested the efficacy of exosomes secreted from HUCB-MSCs under standard culture conditions on post-stroke brain damage and neurological outcome in a rat model of ischemic stroke by performing TTC staining as well as the modified neurological severity scores, modified adhesive removal, beam-walking, and accelerating Rotarod performance tests before ischemia and at regular intervals until seven days reperfusion.

Results: Exosomes treatment attenuated the infarct size. Treatment with exosomes did not affect the post-stroke survival rate and body weight changes, but exacerbated the somatosensory and motor dysfunction and adversely affected the natural recovery that occurs without any treatment.

Conclusion: Treatment with exosomes secreted from HUCB-MSCs under standard culture conditions attenuates the ischemic brain damage but does not improve the post-stroke neurological outcome.

Keywords: Exosomes; Ischemia; Recovery; Reperfusion; Stem cells; Stroke.

MeSH terms

  • Animals
  • Brain / pathology*
  • Brain / physiopathology
  • Cell Line
  • Disease Models, Animal
  • Exosomes / transplantation*
  • Male
  • Mesenchymal Stem Cells / cytology*
  • Motor Activity
  • Rats, Sprague-Dawley
  • Stroke / pathology
  • Stroke / physiopathology
  • Stroke / therapy*
  • Treatment Outcome