Transfer of miR-877-3p via extracellular vesicles derived from dental pulp stem cells attenuates neuronal apoptosis and facilitates early neurological functional recovery after cerebral ischemia-reperfusion injury through the Bclaf1/p53 signaling pathway

  • Pharmacol Res. 2024 Jun 13:107266. doi: 10.1016/j.phrs.2024.107266.
Yan Miao  1 ,  Xin Liang  2 ,  Jigang Chen  3 ,  Hongyi Liu  4 ,  Zilong He  5 ,  Yongkai Qin  5 ,  Aihua Liu  6 ,  Ruxu Zhang  7
Affiliations
  • 1. Department of Neurology, The Third Xiangya Hospital, Central South University, 410013, China.
  • 2. Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, 100038, China.
  • 3. Department of burn and plastic surgery, Beijing Children's Hospital, Capital Medical University, 100045, China.
  • 4. Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, 100070, China; School of Biomedical Engineering, Capital Medical University, Beijing, 100069, China.
  • 5. Department of Neurosurgery, The Third Xiangya Hospital, Central South University, 410013, China.
  • 6. Beijing Neurosurgical Institute, Beijing Tiantan Hospital, Capital Medical University, 100070, China; Department of Neurosurgery, The Third Xiangya Hospital, Central South University, 410013, China. Electronic address: [email protected].
  • 7. Department of Neurology, The Third Xiangya Hospital, Central South University, 410013, China. Electronic address: [email protected].
PMID: 38878918 DOI: 10.1016/j.phrs.2024.107266
Abstract

Cerebral ischemia-reperfusion injury (I/RI) is one of the principal pathogenic factors in the poor prognosis of ischemic stroke, for which current therapeutic options to enhance neurological recovery are notably insufficient. Dental pulp stem cell-derived extracellular vesicles (DPSC-EVs) have promising prospects in stroke treatment and the specific underlying mechanisms have yet to be fully elucidated. The present study observed that DPSC-EVs ameliorated the degree of cerebral edema and infarct volume by reducing the Apoptosis of neurons. Furthermore, the miRNA Sequencing and functional enrichment analysis identified that miR-877-3p as a key component in DPSC-EVs, contributing to neuroprotection and anti-apoptotic effects. Following target prediction and dual-luciferase assay indicated that miR-877-3p interacted with Bcl-2-associated transcription factor (Bclaf1) to play a function. The miR-877-3p inhibitor or Bclaf1 overexpression reversed the neuroprotective effects of DPSC-EVs. The findings reveal a novel therapeutic pathway where miR-877-3p, transferred via DPSC-EVs, confers neuroprotection against cerebral I/RI, highlighting its potential in promoting neuronal survival and recovery post-ischemia.

Keywords
apoptosis; dental pulp stem cell; extracellular vesicles; ischemia–reperfusion injury.
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