Erythropoietin Modification Enhances the Protection of Mesenchymal Stem Cells on Diabetic Rat-Derived Schwann Cells: Implications for Diabetic Neuropathy

Biomed Res Int. 2017;2017:6352858. doi: 10.1155/2017/6352858. Epub 2017 Feb 19.

Abstract

Diabetes-triggered apoptosis of Schwann cells (SC) contributes to the degradation of diabetic peripheral neuropathy (DNP). In recent years, mesenchymal stem cells (MSC) were applied to DPN repair and it was demonstrated that paracrine secretion played a key role in neuroprotection exerted by MSC. Erythropoietin (EPO) is a potent cytokine capable of reducing apoptosis of SC. However, the expression of EPO in MSC is limited. In this study, we hypothesized that overexpression of EPO in MSC (EPO-MSC) may significantly improve their neuroprotective potentials. The EPO overexpression in MSC was achieved by lentivirus transduction. SC derived from the periphery nerve of diabetic rats were cocultured with MSC or EPO-MSC in normal or high glucose culture condition, respectively. In normal glucose culture condition, the overexpression of EPO in MSC promoted the MSC-induced restoration of SC from diabetic rats, including increases in GSH level and cell viability, decrease in TUNEL apoptosis, upregulation of antiapoptotic proteins, p-Akt, and Bcl-2, and downregulation of proapoptotic proteins, cleaved caspase-3, and Bax. The subsequent results in high glucose culture condition showed similar promotions achieved by EPO-MSC. Thus, it could be concluded that EPO-MSC possessed a potent potential in hampering apoptosis of SC, and the suppression was probably attributed to attenuating oxidative stress and regulating apoptosis related protein factors.

MeSH terms

  • Animals
  • Apoptosis
  • Caspase 3 / metabolism
  • Cell Survival
  • Coculture Techniques
  • Diabetes Mellitus, Experimental / therapy*
  • Diabetic Nephropathies / therapy*
  • Erythropoietin / genetics
  • Erythropoietin / metabolism*
  • Glutathione / metabolism
  • Mesenchymal Stem Cells / cytology*
  • Oxidative Stress
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Schwann Cells / cytology*
  • Transduction, Genetic
  • Up-Regulation
  • bcl-2-Associated X Protein / metabolism

Substances

  • Bax protein, rat
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Erythropoietin
  • Akt1 protein, rat
  • Proto-Oncogene Proteins c-akt
  • Casp3 protein, rat
  • Caspase 3
  • Glutathione