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

• We assessed the therapeutic effect of iPSCs in experimental ICH rat.
• Therapeutic effects of iPSCs in rat ICH model were observed.
• The grafted iPSCs exhibited neural cell-specific biomarkers in the brain of ICH rats.
• The levels of BDNF and VEGF were enhanced in the surrounding region of hematoma.
• Functional improvement is partially due to neuronal replacement and neurophic factors.

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.