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Stem Cell Reports. 2014 Mar 6;2(3):337-50. doi: 10.1016/j.stemcr.2014.01.013. eCollection 2014 Mar 11.

Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation.

Author information

1
Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, Japan.
2
Group for Neuronal Differentiation and Development, KAN Research Institute, Inc., 650-0047 Kobe, Japan.
3
Laboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, 565-0871 Osaka, Japan.
4
Department of Reprogramming Science, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, Japan.
5
Department of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, 221 84 Lund, Sweden.
6
Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, Japan ; Department of Biological Repair, Institute for Frontier Medical Sciences, Kyoto University, 606-8507 Kyoto, Japan ; Department of Neurosurgery, Kyoto University School of Medicine, 606-8507 Kyoto, Japan.

Abstract

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.

PMID:
24672756
PMCID:
PMC3964289
DOI:
10.1016/j.stemcr.2014.01.013
[Indexed for MEDLINE]
Free PMC Article
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