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.
| Original language | English |
|---|---|
| Pages (from-to) | 547-558 |
| Number of pages | 12 |
| Journal | Restorative Neurology and Neuroscience |
| Volume | 32 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 2014 |
| Externally published | Yes |
Keywords
- Stroke
- aging
- inflammation
- neural stem cell
- neuroregeneration
- recovery
- reprogramming
- transplantation
ASJC Scopus subject areas
- Neurology
- Developmental Neuroscience
- Clinical Neurology