Human-induced pluripotent stem cells form functional neurons and improve recovery after grafting in stroke-damaged brain

Koichi Oki, Jemal Tatarishvili, James Wood, Philipp Koch, Somsak Wattananit, Yutaka Mine, Emanuela Monni, Daniel Tornero, Henrik Ahlenius, Julia Ladewig, Oliver Brüstle, Olle Lindvall, Zaal Kokaia

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185 Citations (Scopus)

Abstract

Reprogramming of adult human somatic cells to induced pluripotent stem cells (iPSCs) is a novel approach to produce patient-specific cells for autologous transplantation. Whether such cells survive long-term, differentiate to functional neurons, and induce recovery in the stroke-injured brain are unclear. We have transplanted long-term self-renewing neuroepithelial-like stem cells, generated from adult human fibroblast-derived iPSCs, into the stroke-damaged mouse and rat striatum or cortex. Recovery of forepaw movements was observed already at 1 week after transplantation. Improvement was most likely not due to neuronal replacement but was associated with increased vascular endothelial growth factor levels, probably enhancing endogenous plasticity. Transplanted cells stopped proliferating, could survive without forming tumors for at least 4 months, and differentiated to morphologically mature neurons of different subtypes. Neurons in intrastriatal grafts sent axonal projections to the globus pallidus. Grafted cells exhibited electrophysiological properties of mature neurons and received synaptic input from host neurons. Our study provides the first evidence that transplantation of human iPSC-derived cells is a safe and efficient approach to promote recovery after stroke and can be used to supply the injured brain with new neurons for replacement.

Original languageEnglish
Pages (from-to)1120-1133
Number of pages14
JournalStem Cells
Volume30
Issue number6
DOIs
Publication statusPublished - 2012 Jun 1

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Keywords

  • Human
  • Pluripotent
  • Stem cell
  • Stroke
  • Transplantation

ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

Cite this

Oki, K., Tatarishvili, J., Wood, J., Koch, P., Wattananit, S., Mine, Y., Monni, E., Tornero, D., Ahlenius, H., Ladewig, J., Brüstle, O., Lindvall, O., & Kokaia, Z. (2012). Human-induced pluripotent stem cells form functional neurons and improve recovery after grafting in stroke-damaged brain. Stem Cells, 30(6), 1120-1133. https://doi.org/10.1002/stem.1104