title: Human-induced pluripotent stem cells form functional neurons and improve recovery after grafting in stroke-damaged brain.
abstract: Reprogramming of adult human somatic cells to induced pluripotent stem cells (iPSCs) is a novel approach to produce patient-specific cells for autologous transplantation. Whether such cells survive long-term, differentiate to functional neurons, and induce recovery in the stroke-injured brain are unclear. We have transplanted long-term self-renewing neuroepithelial-like stem cells, generated from adult human fibroblast-derived iPSCs, into the stroke-damaged mouse and rat striatum or cortex. Recovery of forepaw movements was observed already at 1 week after transplantation. Improvement was most likely not due to neuronal replacement but was associated with increased vascular endothelial growth factor levels, probably enhancing endogenous plasticity. Transplanted cells stopped proliferating, could survive without forming tumors for at least 4 months, and differentiated to morphologically mature neurons of different subtypes. Neurons in intrastriatal grafts sent axonal projections to the globus pallidus. Grafted cells exhibited electrophysiological properties of mature neurons and received synaptic input from host neurons. Our study provides the first evidence that transplantation of human iPSC-derived cells is a safe and efficient approach to promote recovery after stroke and can be used to supply the injured brain with new neurons for replacement.
authors.affiliation: Laboratory of Neural Stem Cell Biology and Therapy, University Hospital, Lund, Sweden.
authors.forename: Koichi
authors.initials: K
authors.lastname: Oki
authors.forename: Jemal
authors.initials: J
authors.lastname: Tatarishvili
authors.forename: James
authors.initials: J
authors.lastname: Wood
authors.forename: Philipp
authors.initials: P
authors.lastname: Koch
authors.forename: Somsak
authors.initials: S
authors.lastname: Wattananit
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Mine
authors.forename: Emanuela
authors.initials: E
authors.lastname: Monni
authors.forename: Daniel
authors.initials: D
authors.lastname: Tornero
authors.forename: Henrik
authors.initials: H
authors.lastname: Ahlenius
authors.forename: Julia
authors.initials: J
authors.lastname: Ladewig
authors.forename: Oliver
authors.initials: O
authors.lastname: Brüstle
authors.forename: Olle
authors.initials: O
authors.lastname: Lindvall
authors.forename: Zaal
authors.initials: Z
authors.lastname: Kokaia
mesh_terms: D000368:Aged; D000818:Animals; D001921:Brain / Q000166:cytology / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000637:transplantation*; D051379:Mice; D009474:Neurons / Q000166:cytology*; D051381:Rats; D033581:Stem Cell Transplantation / Q000379:methods*; D020521:Stroke / Q000473:pathology* / Q000601:surgery*