Dental pulp stem cell transplantation facilitates neuronal neuroprotection following cerebral ischemic stroke

Biomed Pharmacother. 2022 Aug:152:113234. doi: 10.1016/j.biopha.2022.113234. Epub 2022 Jun 9.

Abstract

Objectives: This study aimed to identify and evaluate the intracranial transplantation of dental pulp stem cells (DPSCs) as a possible ischemic stroke therapy that mitigates neuronal death/apoptosis.

Materials and methods: DPSCs were isolated from the impacted third molars of healthy volunteers and then intracranially injected at 24 h post-ischemic stroke to Sprague Dawley rats that had been subjected to 2 h of middle cerebral artery occlusion. Neurological functional deficits were assessed using the modified neurological severity score (mNSS), and cerebral edema was quantified using brain water content. Neuronal death/apoptosis was indicated by TdT-mediated dUTP Nick-End Labeling (TUNEL) staining, NeuN immunofluorescence and immunohistochemistry, and Western blot analysis of the protein expression of anti-apoptotic indicator of Bcl-2 and apoptotic indicators of Bax and caspase 3.

Results: DPSC transplantation could ameliorate neurological dysfunction and brain edema, reduce infarct volume, decrease the percentage of TUNEL-positive nuclei, increase the number and percentage of NeuN-positive cells in ischemic penumbra, increase the ratio of Bcl-2 and Bax and down-regulate the production of caspase 3 in the cortical infarct zone.

Conclusions: DPSC therapy via intracranial injection exerted remarkably neuroprotection mainly by inhibiting neuronal death/apoptosis.

Keywords: Dental pulp stem cells; Ischemic stroke; Neuronal survival; Neuroprotection; Transplantation.

MeSH terms

  • Animals
  • Brain Edema* / therapy
  • Brain Ischemia* / metabolism
  • Brain Ischemia* / therapy
  • Caspase 3 / metabolism
  • Dental Pulp / metabolism
  • Humans
  • Infarction, Middle Cerebral Artery / therapy
  • Ischemia
  • Ischemic Stroke*
  • Neuroprotection
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Stem Cell Transplantation
  • Stroke* / therapy
  • bcl-2-Associated X Protein / metabolism

Substances

  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Caspase 3