Neurotrophin-3 gene-modified Schwann cells promote TrkC gene-modified mesenchymal stem cells to differentiate into neuron-like cells in poly(lactic-acid-co-glycolic acid) multiple-channel conduit

Cells Tissues Organs. 2012;195(4):313-22. doi: 10.1159/000327724. Epub 2011 Aug 9.

Abstract

Rapid progress in the field of nerve tissue engineering has opened up the way for new therapeutic strategies for spinal cord injury (SCI). Bone marrow-derived mesenchymal stem cells (MSCs) could be differentiated into neural lineages, which can be used as a potential cell source for nerve repair. Schwann cells (SCs) have been reported to support structural and functional recovery of SCI. In this study, we co-cultured neurotrophin-3 (NT-3) gene-modified SCs and NT-3 receptor tyrosine protein kinase C (TrkC) gene-modified MSCs in a three-dimensional porous poly(lactic-acid-co-glycolic acid) (PLGA) conduit with multiple channels in vitro for 14 days. Our results showed that more than 50% of the grafted MSCs were MAP2- and β-III-tubulin-positive cells, and the MSCs expressed a high level of β-III-tubulin detected by Western blotting, indicating a high rate of neuronal differentiation. Furthermore, immunostaining of PSD95 revealed the formation of a synapse-like structure, which was confirmed under electron microscopy. In conclusion, co-culture of NT-3 gene-modified SCs and TrkC gene-modified MSCs in the PLGA multiple-channeled conduit can promote MSCs' differentiation into neuron-like cells with synaptogenesis potential. Our study provides a biological basis for future application of this artificial MSCs/SCs/PLGA complex in the SCI treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Biomarkers / metabolism
  • Cell Differentiation / drug effects*
  • Coculture Techniques
  • Gene Expression Regulation / drug effects
  • Green Fluorescent Proteins / metabolism
  • Lactic Acid / pharmacology*
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mesenchymal Stem Cells / metabolism
  • Microscopy, Electron, Scanning
  • Neural Stem Cells / cytology
  • Neural Stem Cells / drug effects
  • Neural Stem Cells / metabolism
  • Neurogenesis / drug effects
  • Neurons / cytology*
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurotrophin 3 / genetics*
  • Neurotrophin 3 / metabolism
  • Polyglycolic Acid / pharmacology*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Rats
  • Rats, Sprague-Dawley
  • Receptor, trkC / genetics*
  • Receptor, trkC / metabolism
  • Schwann Cells / cytology
  • Schwann Cells / drug effects
  • Schwann Cells / metabolism*
  • Synapses / drug effects
  • Synapses / metabolism
  • Tissue Scaffolds

Substances

  • Biomarkers
  • Neurotrophin 3
  • Green Fluorescent Proteins
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Lactic Acid
  • Receptor, trkC