Isolation of Human Induced Pluripotent Stem Cell-Derived Dopaminergic Progenitors by Cell Sorting for Successful Transplantation
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 pr...
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doaj-34a783828aef48b59155490b89d26cac2020-11-24T21:32:44ZengElsevierStem Cell Reports2213-67112014-03-012333735010.1016/j.stemcr.2014.01.013Isolation of Human Induced Pluripotent Stem Cell-Derived Dopaminergic Progenitors by Cell Sorting for Successful TransplantationDaisuke Doi0Bumpei Samata1Mitsuko Katsukawa2Tetsuhiro Kikuchi3Asuka Morizane4Yuichi Ono5Kiyotoshi Sekiguchi6Masato Nakagawa7Malin Parmar8Jun Takahashi9Department of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, JapanDepartment of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, JapanDepartment of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, JapanDepartment of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, JapanDepartment of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, JapanGroup for Neuronal Differentiation and Development, KAN Research Institute, Inc., 650-0047 Kobe, JapanLaboratory of Extracellular Matrix Biochemistry, Institute for Protein Research, Osaka University, 565-0871 Osaka, JapanDepartment of Reprogramming Science, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, JapanDepartment of Experimental Medical Science, Wallenberg Neuroscience Center, Lund University, 221 84 Lund, SwedenDepartment of Clinical Application, Center for iPS Cell Research and Application, Kyoto University, 606-8507 Kyoto, JapanHuman 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.http://www.sciencedirect.com/science/article/pii/S2213671114000307 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Daisuke Doi Bumpei Samata Mitsuko Katsukawa Tetsuhiro Kikuchi Asuka Morizane Yuichi Ono Kiyotoshi Sekiguchi Masato Nakagawa Malin Parmar Jun Takahashi |
spellingShingle |
Daisuke Doi Bumpei Samata Mitsuko Katsukawa Tetsuhiro Kikuchi Asuka Morizane Yuichi Ono Kiyotoshi Sekiguchi Masato Nakagawa Malin Parmar Jun Takahashi Isolation of Human Induced Pluripotent Stem Cell-Derived Dopaminergic Progenitors by Cell Sorting for Successful Transplantation Stem Cell Reports |
author_facet |
Daisuke Doi Bumpei Samata Mitsuko Katsukawa Tetsuhiro Kikuchi Asuka Morizane Yuichi Ono Kiyotoshi Sekiguchi Masato Nakagawa Malin Parmar Jun Takahashi |
author_sort |
Daisuke Doi |
title |
Isolation of Human Induced Pluripotent Stem Cell-Derived Dopaminergic Progenitors by Cell Sorting for Successful Transplantation |
title_short |
Isolation of Human Induced Pluripotent Stem Cell-Derived Dopaminergic Progenitors by Cell Sorting for Successful Transplantation |
title_full |
Isolation of Human Induced Pluripotent Stem Cell-Derived Dopaminergic Progenitors by Cell Sorting for Successful Transplantation |
title_fullStr |
Isolation of Human Induced Pluripotent Stem Cell-Derived Dopaminergic Progenitors by Cell Sorting for Successful Transplantation |
title_full_unstemmed |
Isolation of Human Induced Pluripotent Stem Cell-Derived Dopaminergic Progenitors by Cell Sorting for Successful Transplantation |
title_sort |
isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation |
publisher |
Elsevier |
series |
Stem Cell Reports |
issn |
2213-6711 |
publishDate |
2014-03-01 |
description |
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. |
url |
http://www.sciencedirect.com/science/article/pii/S2213671114000307 |
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