1. Academic Validation
  2. 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

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

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: liuaihuadoctor@163.com.
  • 7 Department of Neurology, The Third Xiangya Hospital, Central South University, 410013, China. Electronic address: zhangruxu@vip.163.com.
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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