Implantation of Endothelial Cells with Mesenchymal Stem Cells Accelerates Dental Pulp Tissue Regeneration/Healing in Pulpotomized Rat Molars

J Endod. 2017 Jun;43(6):943-948. doi: 10.1016/j.joen.2017.01.035. Epub 2017 Apr 14.

Abstract

Introduction: This study aimed to examine whether the implantation of mesenchymal stem cells (MSCs) with endothelial cells (ECs) accelerates pulp tissue regeneration/healing and induces dentin bridge formation in a rat model of molar coronal pulp regeneration.

Methods: The maxillary first molars of Wistar rats were subjected to pulpotomy. Then, pulp chambers were implanted with biodegradable hydrogel-made scaffolds carrying MSCs together or without dermal microvascular ECs, and the cavities were sealed with mineral trioxide aggregate. After 14 days, pulp samples were analyzed by immunohistochemistry; messenger RNA expression of B-cell lymphoma 2 (Bcl-2), chemokine (C-X-C motif) ligand 1 (Cxcl1), CXC receptor 2 (Cxcr2), and dentin sialophosphoprotein (Dspp) by quantitative polymerase chain reaction, and protein expression of nestin and vascular endothelial growth factor by Western blotting.

Results: Teeth coimplanted with MSCs and ECs showed pulp healing with complete dentin bridge formation, whereas those implanted with MSCs alone had incomplete dentin bridges. Bcl-2, Cxcl1, Cxcr2, and Dspp messenger RNA levels were significantly up-regulated in the pulp of MSC/EC-implanted teeth compared with those in MSC-implanted teeth. Immunohistochemical analysis revealed the expression of nestin in odontoblastlike cells under dentin bridges in the MSC/EC coimplanted group. The density of CD31-expressing ECs and the expression of nestin and vascular endothelial growth factor proteins were significantly up-regulated in the MSC/EC-implanted pulp compared with the MSC-implanted pulp.

Conclusions: The implantation of ECs with MSCs accelerated pulp tissue regeneration/healing and dentin bridge formation, up-regulated the expression of proangiogenic factors, and increased the density of ECs in pulpotomized rat molars.

Keywords: Angiogenesis; endothelial cells; mesenchymal stem cells; rat dental pulp; tissue engineering.

MeSH terms

  • Aluminum Compounds / therapeutic use
  • Animals
  • Calcium Compounds / therapeutic use
  • Dental Pulp / physiology*
  • Drug Combinations
  • Endothelial Cells / transplantation*
  • Female
  • Guided Tissue Regeneration / methods
  • Mesenchymal Stem Cell Transplantation*
  • Molar / physiology*
  • Oxides / therapeutic use
  • Pulpotomy
  • Rats
  • Rats, Wistar
  • Regeneration / physiology*
  • Silicates / therapeutic use
  • Tissue Scaffolds

Substances

  • Aluminum Compounds
  • Calcium Compounds
  • Drug Combinations
  • Oxides
  • Silicates
  • mineral trioxide aggregate