1. Human induced pluripotent stem cells improve recovery in stroke-injured aged rats.
- Author
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Tatarishvili, Jemal, Oki, Koichi, Monni, Emanuela, Koch, Philipp, Memanishvili, Tamar, Buga, Ana-Maria, Verma, Vivek, Popa-Wagner, Aurel, Brüstle, Oliver, Lindvall, Olle, and Kokaia, Zaal
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PLURIPOTENT stem cells , *NEURONS , *FIBROBLASTS , *STROKE , *CEREBRAL arteries , *CELL proliferation , *BIOMARKERS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2014
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