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

研究成果: Article

192 引用 (Scopus)

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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.

元の言語English
ページ(範囲)1120-1133
ページ数14
ジャーナルStem Cells
30
発行部数6
DOI
出版物ステータスPublished - 2012 6 1

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ASJC Scopus subject areas

  • Molecular Medicine
  • Developmental Biology
  • Cell Biology

これを引用

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