Human induced pluripotent stem cells improve recovery in stroke-injured aged rats

Jemal Tatarishvili, Koichi Oki, Emanuela Monni, Philipp Koch, Tamar Memanishvili, Ana Maria Buga, Vivek Verma, Aurel Popa-Wagner, Oliver Brüstle, Olle Lindvall, Zaal Kokaia

Research output: Contribution to journalArticle

49 Citations (Scopus)

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 languageEnglish
Pages (from-to)547-558
Number of pages12
JournalRestorative Neurology and Neuroscience
Volume32
Issue number4
DOIs
Publication statusPublished - 2014 Jan 1

Keywords

  • Stroke
  • aging
  • inflammation
  • neural stem cell
  • neuroregeneration
  • recovery
  • reprogramming
  • transplantation

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology

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    Tatarishvili, J., Oki, K., Monni, E., Koch, P., Memanishvili, T., Buga, A. M., Verma, V., Popa-Wagner, A., Brüstle, O., Lindvall, O., & Kokaia, Z. (2014). Human induced pluripotent stem cells improve recovery in stroke-injured aged rats. Restorative Neurology and Neuroscience, 32(4), 547-558. https://doi.org/10.3233/RNN-140404