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

43 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
Externally publishedYes

Fingerprint

Induced Pluripotent Stem Cells
Stroke
Brain
Stem Cells
Neurons
GABAergic Neurons
Aptitude
Middle Cerebral Artery Infarction
Microglia
Rodentia
Macrophages
Cell Proliferation
Survival

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience
  • Clinical Neurology
  • Medicine(all)

Cite this

Tatarishvili, J., Oki, K., Monni, E., Koch, P., Memanishvili, T., Buga, A. M., ... 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

Human induced pluripotent stem cells improve recovery in stroke-injured aged rats. / Tatarishvili, Jemal; Oki, Koichi; Monni, Emanuela; Koch, Philipp; Memanishvili, Tamar; Buga, Ana Maria; Verma, Vivek; Popa-Wagner, Aurel; Brüstle, Oliver; Lindvall, Olle; Kokaia, Zaal.

In: Restorative Neurology and Neuroscience, Vol. 32, No. 4, 2014, p. 547-558.

Research output: Contribution to journalArticle

Tatarishvili, J, Oki, K, Monni, E, Koch, P, Memanishvili, T, Buga, AM, 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, vol. 32, no. 4, pp. 547-558. https://doi.org/10.3233/RNN-140404
Tatarishvili, Jemal ; Oki, Koichi ; Monni, Emanuela ; Koch, Philipp ; Memanishvili, Tamar ; Buga, Ana Maria ; Verma, Vivek ; Popa-Wagner, Aurel ; Brüstle, Oliver ; Lindvall, Olle ; Kokaia, Zaal. / Human induced pluripotent stem cells improve recovery in stroke-injured aged rats. In: Restorative Neurology and Neuroscience. 2014 ; Vol. 32, No. 4. pp. 547-558.
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