Transplantation of CX3CL1-expressing mesenchymal stem cells provides neuroprotective and immunomodulatory effects in a rat model of retinal degeneration

Ocul Immunol Inflamm. 2013 Aug;21(4):276-85. doi: 10.3109/09273948.2013.791925. Epub 2013 May 29.

Abstract

Purpose: To investigate the neuroprotective and immunomodulatory effects of mesenchymal stem cells (MSCs) engineered to secrete CX3CL1 on the light-injured retinal structure and function.

Methods: Normal MSCs and CX3CL1-expressing MSCs (CX3CL1-MSCs) were transplanted into the subretinal space of light-injured rats. By ERG and TUNEL methods, their rescue effect of the host retina was compared with untreated light-injured and vehicle-injected rats. Activated microglia in the retina were stained by ED-1 antibody, and Western blot was performed to quantify cytokines secreted by the retina post-transplantation.

Results: ERG analysis showed better function in CX3CL1-MSC-injected group than other groups at 21 days after transplantation (p < 0.05). CX3CL1-MSCs inhibited apoptosis of the retinal cells and microglial activation. Neurotrophic factors expression in host retina that received CX3CL1-MSCs was stronger than in the retina that received normal MSCs. Conversely, the expression of proinflammatory factors was downregulated.

Conclusions: CX3CL1-MSCs subretinal transplantation may enhance protective effect against light-induced retinal degeneration.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Blotting, Western
  • Cells, Cultured
  • Chemokine CX3CL1 / biosynthesis
  • Chemokine CX3CL1 / genetics*
  • DNA / genetics*
  • Disease Models, Animal
  • Electroretinography
  • Gene Expression Regulation*
  • Immunohistochemistry
  • Immunomodulation / genetics*
  • In Situ Nick-End Labeling
  • Male
  • Mesenchymal Stem Cell Transplantation / methods*
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Photoreceptor Cells, Vertebrate / metabolism
  • Photoreceptor Cells, Vertebrate / pathology
  • Polymerase Chain Reaction
  • Rats
  • Rats, Sprague-Dawley
  • Retinal Degeneration / genetics
  • Retinal Degeneration / immunology
  • Retinal Degeneration / surgery*

Substances

  • Chemokine CX3CL1
  • Cx3cl1 protein, rat
  • DNA