Transplantation of mesenchymal stem cells overexpressing interleukin-10 induces autophagy response and promotes neuroprotection in a rat model of TBI

Panchanan Maiti, Sarah Peruzzaro, Nivya Kolli, Melissa Andrews, Abeer Al-Gharaibeh, Julien Rossignol, Gary L. Dunbar

Research output: Contribution to journalArticlepeer-review

28 Scopus citations

Abstract

Autophagy, including mitophagy, is critical for neuroprotection in traumatic brain injury (TBI). Transplantation of mesenchymal stem cells (MSCs) provides neuroprotection and induces autophagy by increasing anti-inflammatory cytokines, such as interleukin-10 (IL-10). To evaluate these effects of IL10 that are released by MSCs, we genetically engineered MSCs to overexpress IL10 and compared their effects to unaltered MSCs following transplantation near the site of induced TBIs in rats. Adult, male Sprague-Dawley rats were divided into four groups: Sham + vehicle, TBI + vehicle, TBI + MSCs-IL-10 and TBI + MSCs-GFP. Thirty-six hours post-TBI, the first two groups received vehicle (Hanks balance salt solution), whereas last two groups were transplanted with MSCs-IL-10 or MSCs-GFP. Three weeks after transplantation, biomarkers for neurodegenerative changes, autophagy, mitophagy, cell death and survival markers were measured. We observed a significant increase in the number of dead cells in the cortex and hippocampus in TBI rats, whereas transplantation of MSCs-IL-10 significantly reduced their numbers in comparison to MSCs alone. MSCs-IL-10 rats had increased autophagy, mitophagy and cell survival markers, along with decreased markers for cell death and neuroinflammation. These results suggest that transplantation of MSCs-IL-10 may be an effective strategy to protect against TBI-induced neuronal damage.

Original languageEnglish
Pages (from-to)5211-5224
Number of pages14
JournalJournal of Cellular and Molecular Medicine
Volume23
Issue number8
DOIs
StatePublished - Aug 2019

Keywords

  • IL-10 overexpressed MSCs
  • TBI
  • autophagy markers
  • neuroinflammation

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