Neuronal Differentiation of Human Mesenchymal Stem Cells Using Exosomes Derived from Differentiating Neuronal Cells

PLoS One. 2015 Aug 6;10(8):e0135111. doi: 10.1371/journal.pone.0135111. eCollection 2015.

Abstract

Exosomes deliver functional proteins and genetic materials to neighboring cells, and have potential applications for tissue regeneration. One possible mechanism of exosome-promoted tissue regeneration is through the delivery of microRNA (miRNA). In this study, we hypothesized that exosomes derived from neuronal progenitor cells contain miRNAs that promote neuronal differentiation. We treated mesenchymal stem cells (MSCs) daily with exosomes derived from PC12 cells, a neuronal cell line, for 1 week. After the treatment with PC12-derived exosomes, MSCs developed neuron-like morphology, and gene and protein expressions of neuronal markers were upregulated. Microarray analysis showed that the expression of miR-125b, which is known to play a role in neuronal differentiation of stem cells, was much higher in PC12-derived exosomes than in exosomes from B16-F10 melanoma cells. These results suggest that the delivery of miRNAs contained in PC12-derived exosomes is a possible mechanism explaining the neuronal differentiation of MSC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow Cells / cytology
  • Bone Marrow Cells / drug effects*
  • Bone Marrow Cells / metabolism
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • Culture Media, Conditioned / chemistry
  • Culture Media, Conditioned / pharmacology*
  • Exosomes / chemistry*
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Humans
  • Melanoma, Experimental / chemistry
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / drug effects*
  • Mesenchymal Stem Cells / metabolism
  • Mice
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Oligonucleotide Array Sequence Analysis
  • PC12 Cells
  • Primary Cell Culture
  • Rats

Substances

  • Culture Media, Conditioned
  • MIRN125 microRNA, human
  • MicroRNAs

Grants and funding

QX received a grant from The Pew Charitable Trusts (http://www.pewtrusts.org/). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.