Jemal Tatarishvili1, Koichi Oki1, Emanuela Monni1, Philipp Koch2, Tamar Memanishvili3, Ana-Maria Buga4, Vivek Verma1, Aurel Popa-Wagner4, Oliver Brüstle2, Olle Lindvall1, Zaal Kokaia1. 1. Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, Lund, Sweden. 2. Institute of Reconstructive Neurobiology, Life & Brain Center, University of Bonn and Hertie Fundation, Bonn, Germany. 3. Laboratory of Stem Cells and Restorative Neurology, Lund Stem Cell Center, University Hospital, Lund, Sweden I. Javakhishvili Tbilisi State University, Tbilisi, Georgia. 4. Department of Psychiatry and Molecular Psychiatry, Rostock University Medical School, Rostock, Germany.
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.
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.
Authors: Helen K Smith; Seiichi Omura; Shantel A Vital; Felix Becker; Elena Y Senchenkova; Gaganpreet Kaur; Ikuo Tsunoda; Shayn M Peirce; Felicity N E Gavins Journal: FASEB J Date: 2017-12-21 Impact factor: 5.191
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