Stem Cell Reports
Volume 2, Issue 3, 11 March 2014, Pages 337-350
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Article
Isolation of Human Induced Pluripotent Stem Cell-Derived Dopaminergic Progenitors by Cell Sorting for Successful Transplantation

https://doi.org/10.1016/j.stemcr.2014.01.013Get rights and content
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Highlights

  • DA neurons were highly efficiently induced from iPSCs on xeno-free laminin fragment

  • DA progenitors were enriched by sorting of CORIN+ cells

  • CORIN+ cell grafts resulted in good DA neuron survival without tumor formation

  • NURR1+ cell-dominant stage exhibited the best survival and function as DA neurons

Summary

Human induced pluripotent stem cells (iPSCs) can provide a promising source of midbrain dopaminergic (DA) neurons for cell replacement therapy for Parkinson’s disease. However, iPSC-derived donor cells inevitably contain tumorigenic or inappropriate cells. Here, we show that human iPSC-derived DA progenitor cells can be efficiently isolated by cell sorting using a floor plate marker, CORIN. We induced DA neurons using scalable culture conditions on human laminin fragment, and the sorted CORIN+ cells expressed the midbrain DA progenitor markers, FOXA2 and LMX1A. When transplanted into 6-OHDA-lesioned rats, the CORIN+ cells survived and differentiated into midbrain DA neurons in vivo, resulting in significant improvement of the motor behavior, without tumor formation. In particular, the CORIN+ cells in a NURR1+ cell-dominant stage exhibited the best survival and function as DA neurons. Our method is a favorable strategy in terms of scalability, safety, and efficiency and may be advantageous for clinical application.

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