Schwann cells secrete extracellular vesicles to promote and maintain the proliferation and multipotency of hDPCs

Cell Prolif. 2017 Aug;50(4):e12353. doi: 10.1111/cpr.12353.

Abstract

Objectives: Schwann cells (SCs) are the principal glial cells in peripheral nerve system, involved in neuropathies with great regenerative potential. Dental pulp cells have been reported to maintain neurogenic potential. In contrast, the regulatory role of SCs on human dental pulp cells (hDPCs) development remains undefined.

Materials and methods: SC secretion and SC-derived extracellular vesicles (EVs) were collected and used to treat hDPCs; and proliferation and multiple differentiation of hDPCs were detected after EVs treatments. Finally, we analysed the proteomes of SC-EVs and SCs through mass spectrum.

Results: In this study, we found SC secretion showed a predominantly regulatory role on the development of hDPCs. Further, we identified EVs from SC secretion with similar function as SC secretion in regulating hDPCs proliferation and multipotency. And expression of transcription factor Oct4 was upregulated after treatment of both SC secretion and EVs, as well as Sox2 and Nanog. We detected abundant enrichment of Oct4 in EVs, which might be responsible for the upregulation of stem cell-related genes in hDPCs. Through proteome and western blot analysis, we found enriched TGFβs in EVs, indicating that accelerated hDPCs proliferation may be mediated by activated TGFβ-Samd and TGFβ-MAPK signalling.

Conclusions: In summary, our study sheds light on critical regulatory ability of SC-derived EVs on hDPCs proliferation and multipotency, suggesting great implications for seeding cells used in tissue engineering.

MeSH terms

  • Cell Differentiation
  • Cell Proliferation
  • Cells, Cultured
  • Chromatography, High Pressure Liquid
  • Dental Pulp / cytology
  • Extracellular Vesicles / metabolism*
  • Humans
  • Microscopy, Fluorescence
  • Nanog Homeobox Protein / genetics
  • Nanog Homeobox Protein / metabolism
  • Octamer Transcription Factor-3 / genetics
  • Octamer Transcription Factor-3 / metabolism
  • Proteome / analysis
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism
  • Schwann Cells / cytology
  • Schwann Cells / metabolism*
  • Signal Transduction / drug effects
  • Smad Proteins / metabolism
  • Stem Cells / cytology
  • Stem Cells / metabolism*
  • Tandem Mass Spectrometry
  • Transforming Growth Factor beta / metabolism
  • Up-Regulation

Substances

  • Nanog Homeobox Protein
  • Octamer Transcription Factor-3
  • Proteome
  • SOXB1 Transcription Factors
  • Smad Proteins
  • Transforming Growth Factor beta