期刊
RESTORATIVE NEUROLOGY AND NEUROSCIENCE
卷 32, 期 4, 页码 547-558出版社
IOS PRESS
DOI: 10.3233/RNN-140404
关键词
Stroke; neuroregeneration; inflammation; reprogramming; recovery; neural stem cell; aging; transplantation
资金
- Swedish Research Council
- European Union project TargetBraIn [279017]
- AFA Foundation
- Swedish Government Initiative for Strategic Research Areas (StemTherapy)
- Shota Rustaveli National Science Foundation (Georgia)
Purpose: Induced pluripotent stem cells (iPSCs) improve behavior and form neurons after implantation into the stroke-injured adult rodent brain. How the aged brain responds to grafted iPSCs is unknown. We determined survival and differentiation of grafted human fibroblast-derived iPSCs and their ability to improve recovery in aged rats after stroke. Methods: Twenty-four months old rats were subjected to 30 min distal middle cerebral artery occlusion causing neocortical damage. After 48 h, animals were transplanted intracortically with human iPSC-derived long-term neuroepithelial-like stem (hiPSC-lt-NES) cells. Controls were subjected to stroke and were vehicle-injected. Results: Cell-grafted animals performed better than vehicle-injected recipients in cylinder test at 4 and 7 weeks. At 8 weeks, cell proliferation was low (0.7 %) and number of hiPSC-lt-NES cells corresponded to 49.2% of that of implanted cells. Transplanted cells expressed markers of neuroblasts and mature and GABAergic neurons. Cell-grafted rats exhibited less activated microglia/macrophages in injured cortex and neuronal loss was mitigated. Conclusions: Our study provides the first evidence that grafted human iPSCs survive, differentiate to neurons and ameliorate functional deficits in stroke-injured aged brain.
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