کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6282970 | 1615150 | 2013 | 6 صفحه PDF | دانلود رایگان |
- We reprogrammed ICH patient's skin cells into iPSCs.
- The iPSCs can differentiate into NES cells and neural cells in vitro.
- Therapeutic effects of iPSC-derived NES cells in rat ICH model were observed.
- The grafted NES cells differentiated into neural cells in the brain of ICH rats.
- Functional improvement of ICH rat is partially due to neuronal replacement.
Specific targeted therapy for intracerebral hemorrhage (ICH), which has high disability and case-fatality rate, is currently not available. Induced pluripotent stem cells (iPSCs) generated from somatic cells of ICH patients have therapeutic potential for individualized cerebral protection. While, whether ICH patient-originated iPSCs could differentiate into neuro-epithelial-like stem (NES) cells and whether such NES cells could improve functional recovery in the hemorrhage-injured brain are unclear. Here, we showed that fibroblasts from an ICH patient can be efficiently reprogrammed to iPSCs by lentiviral vectors carrying defined transcription factors (OCT4, SOX2, KLF4, and c-MYC). These iPSCs have the typical morphology, surface antigens, capability of self-renewal and differentiating into cell types of all three embryonic germ layers that are similar to human embryonic stem cells (hESCs). Using defined serum-free neural differentiation medium, we induced the iPSCs differentiate into NES cells. Subsequently, the NES cells from ICH patient-originated iPSCs were transplanted into the perihematoma of rats with experimental ICH injury. Intriguingly, recovery of neurological dysfunction in experimental ICH rats was observed post-NES cells graftage. Transplanted NES cells migrated to the surrounding area of hematoma, survived and differentiated into neuron-like cells. Our study demonstrates that the transplantation of human iPS-originated NES cells is an effective approach of treating ICH injury and the improvement of neural function is partially due to neuronal replacement and regeneration.
Journal: Neuroscience Letters - Volume 548, 26 August 2013, Pages 95-100