Stem cells from wildtype and Friedreich's ataxia mice present similar neuroprotective properties in dorsal root ganglia cells

PLoS One. 2013 May 9;8(5):e62807. doi: 10.1371/journal.pone.0062807. Print 2013.

Abstract

Many neurodegenerative disorders share a common susceptibility to oxidative stress, including Alzheimer's, Parkinson Disease, Huntington Disease and Friedreich's ataxia. In a previous work, we proved that stem cell-conditioned medium increased the survival of cells isolated from Friedreich's ataxia patients, when submitted to oxidative stress. The aim of the present work is to confirm this same effect in dorsal root ganglia cells isolated from YG8 mice, a mouse model of Friedreich's ataxia. In this disorder, the neurons of the dorsal root ganglia are the first to degenerate. Also, in this work we cultured mesenchymal stem cells isolated from YG8 mice, in order to compare them with their wildtype counterpart. To this end, dorsal root ganglia primary cultures isolated from YG8 mice were exposed to oxidative stress and cultured with conditioned medium from either wildtype or YG8 stem cells. As a result, the conditioned medium increased the survival of the dorsal root ganglia cells. This coincided with an increase in oxidative stress-related markers and frataxin expression levels. BDNF, NT3 and NT4 trophic factors were detected in the conditioned medium of both wild-type and YG8 stem cells, all which bind to the various neuronal cell types present in the dorsal root ganglia. No differences were observed in the stem cells isolated from wildtype and YG8 mice. The results presented confirm the possibility that autologous stem cell transplantation may be a viable therapeutic approach in protecting dorsal root ganglia neurons of Friedreich's ataxia patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Brain-Derived Neurotrophic Factor / genetics
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Survival / drug effects
  • Cells, Cultured
  • Culture Media, Conditioned / metabolism*
  • Culture Media, Conditioned / pharmacology
  • Friedreich Ataxia / genetics
  • Friedreich Ataxia / metabolism*
  • Ganglia, Spinal / cytology
  • Gene Expression
  • Humans
  • Hydrogen Peroxide / pharmacology
  • Immunohistochemistry
  • Iron-Binding Proteins / genetics
  • Iron-Binding Proteins / metabolism
  • Mesenchymal Stem Cells / cytology
  • Mesenchymal Stem Cells / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / metabolism
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / metabolism*
  • Neuroprotective Agents / metabolism
  • Neuroprotective Agents / pharmacology
  • Neurotrophin 3 / genetics
  • Neurotrophin 3 / metabolism
  • Oxidants / pharmacology
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Brain-Derived Neurotrophic Factor
  • Culture Media, Conditioned
  • Iron-Binding Proteins
  • Nerve Growth Factors
  • Neuroprotective Agents
  • Neurotrophin 3
  • Oxidants
  • frataxin
  • Hydrogen Peroxide
  • neurotrophin 4

Grant support

This work was supported by FARA (Friedreich’s Ataxia Research Alliance), ASOGAF (Friedreich’s Ataxia association of Granada), Science and Innovation Ministry (MICINN BFU2010-27326), GVA Prometeo grant 2009/028, Tercel (RD06/0010/0023 & RD06/0010/24), MEC-CONSOLIDER CSD2007-00023, Cinco P menos Foundation, EUCOMM, Fundación Diogenes-Elche city government, Walk on Project, and MAPFRE Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.