title: Transplantation of human neuro-epithelial-like stem cells derived from induced pluripotent stem cells improves neurological function in rats with experimental intracerebral hemorrhage.
abstract: 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.
authors.affiliation: Third Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Qin
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.forename: Huili
authors.initials: H
authors.lastname: Zhang
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Wang
authors.forename: Ning
authors.initials: N
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Ji
authors.forename: Jing
authors.initials: J
authors.lastname: Qi
authors.forename: Avinash
authors.initials: A
authors.lastname: Chandra
authors.forename: Bo
authors.initials: B
authors.lastname: Yang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guangming
authors.initials: G
authors.lastname: Gong
authors.forename: Yuming
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002478:Cells, Cultured; D002543:Cerebral Hemorrhage / Q000473:pathology* / Q000601:surgery*; D006801:Humans; D000090062:Kruppel-Like Factor 4; D008297:Male; D008875:Middle Aged; D009416:Nerve Regeneration / Q000502:physiology; D058953:Neural Stem Cells / Q000473:pathology* / Q000637:transplantation*; D039904:Pluripotent Stem Cells / Q000473:pathology* / Q000637:transplantation*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D016896:Treatment Outcome
keywords: Induced pluripotent stem cells (iPSCs); Intracerebral hemorrhage (ICH); Neural differentiation; Neuro-epithelial-like stem (NES) cells