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Human Induced Pluripotent Stem Cells form Functional Neurons and Improve Recovery After Grafting in Stroke-Damaged Brain.

Oki, Koichi LU ; Tatarishvili, Jemal LU ; Woods, James; Koch, Philipp; Wattananit, Somsak LU ; Mine, Yutaka LU ; Monni, Emanuela LU ; Tornero Prieto, Daniel LU ; Ahlenius, Henrik LU and Ladewig, Julia, et al. (2012) In Stem Cells 30(6). p.1120-1133
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 is unclear. We have transplanted long-term self-renewing neuroepithelial-like stem (lt-NES) 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... (More)
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 is unclear. We have transplanted long-term self-renewing neuroepithelial-like stem (lt-NES) 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. (Less)
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published
subject
keywords
Stroke, Stem cell, Pluripotent, Human, Transplantation
in
Stem Cells
volume
30
issue
6
pages
1120 - 1133
publisher
AlphaMed Press
external identifiers
  • wos:000304087300009
  • pmid:22495829
  • scopus:84861903354
ISSN
1549-4918
DOI
10.1002/stem.1104
language
English
LU publication?
yes
id
94728d87-2f25-44fa-9fde-d6e63bc05173 (old id 2519549)
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http://www.ncbi.nlm.nih.gov/pubmed/22495829?dopt=Abstract
date added to LUP
2012-05-06 17:17:48
date last changed
2017-11-19 03:46:33
@article{94728d87-2f25-44fa-9fde-d6e63bc05173,
  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 is unclear. We have transplanted long-term self-renewing neuroepithelial-like stem (lt-NES) 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.},
  author       = {Oki, Koichi and Tatarishvili, Jemal and Woods, James and Koch, Philipp and Wattananit, Somsak and Mine, Yutaka and Monni, Emanuela and Tornero Prieto, Daniel and Ahlenius, Henrik and Ladewig, Julia and Brüstle, Oliver and Lindvall, Olle and Kokaia, Zaal},
  issn         = {1549-4918},
  keyword      = {Stroke,Stem cell,Pluripotent,Human,Transplantation},
  language     = {eng},
  number       = {6},
  pages        = {1120--1133},
  publisher    = {AlphaMed Press},
  series       = {Stem Cells},
  title        = {Human Induced Pluripotent Stem Cells form Functional Neurons and Improve Recovery After Grafting in Stroke-Damaged Brain.},
  url          = {http://dx.doi.org/10.1002/stem.1104},
  volume       = {30},
  year         = {2012},
}