Functional recovery after transplantation of induced pluripotent stem cells in a rat hemorrhagic stroke model

Neurosci Lett. 2013 Oct 25:554:70-5. doi: 10.1016/j.neulet.2013.08.047. Epub 2013 Sep 1.

Abstract

Transplantation of induced pluripotent stem cells (iPSCs) has shown promising therapeutic effects for ischemic stroke. However, it is not clear if this treatment would promote recovery after intracerebral hemorrhage (ICH). In this study, we investigated the functional outcome of iPSCs transplantation in experimental ICH in rats. IPSCs were derived from an ICH patient's fibroblasts and were injected into the ipsilateral side of ICH in rats. IPSCs transplantation significantly improved the neurological functions after ICH as compared to vehicle and fibroblast injection. The grafted iPSCs migrated into brain tissue around the hematoma, survived after 4 weeks of transplantation, and exhibited the neural cell-specific biomarkers nestin, β-tubulin, and GFAP. Immunohistochemical staining showed that the densities of brain derived neurophic factors (BDNF)-positive cells and vascular endothelial growth factor (VEGF)-positive cells were significantly increased around the hemorrhagic brain tissues of iPSCs-treated rats. In addition, iPSCs treatment increased the protein expression of BDNF and VEGF in the surrounding region of hematoma. These findings demonstrate that the transplantation of ICH patient-derived iPSCs contributes toward the improved neurological function in experimental ICH rats. The mechanisms are possibly due to neuronal replacement and enhanced secretion of neurophic factors. Our data suggest that transplantation of ICH patient-derived iPSCs may be a therapeutic strategy for hemorrhagic stroke.

Keywords: Brain derived neurophic factors (BDNF); Induced pluripotent stem cells (iPSCs); Intracerebral hemorrhage (ICH); Vascular endothelial growth factor (VEGF).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / metabolism
  • Brain / pathology
  • Brain-Derived Neurotrophic Factor / metabolism
  • Cell Differentiation
  • Cerebral Hemorrhage / pathology
  • Cerebral Hemorrhage / physiopathology
  • Cerebral Hemorrhage / therapy*
  • Epithelial Cells / cytology
  • Epithelial Cells / transplantation
  • Male
  • Neural Stem Cells / cytology
  • Neural Stem Cells / transplantation*
  • Pluripotent Stem Cells / cytology
  • Pluripotent Stem Cells / transplantation*
  • Rats, Sprague-Dawley
  • Recovery of Function
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Brain-Derived Neurotrophic Factor
  • Vascular Endothelial Growth Factor A