Human Induced Pluripotent Stem Cells form Functional Neurons and Improve Recovery After Grafting in Stroke-Damaged Brain.

Research output: Contribution to journalArticle

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 is unclear. We have transplanted long-term self-renewing neuroepithelial-like stem (lt-NES) 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.

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Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology

Keywords

  • Stroke, Stem cell, Pluripotent, Human, Transplantation
Original languageEnglish
Pages (from-to)1120-1133
JournalStem Cells
Volume30
Issue number6
Publication statusPublished - 2012
Publication categoryResearch
Peer-reviewedYes