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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964289/ https://www.ncbi.nlm.nih.gov/pubmed/24672756 http://dx.doi.org/10.1016/j.stemcr.2014.01.013 |
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author | Doi, Daisuke Samata, Bumpei Katsukawa, Mitsuko Kikuchi, Tetsuhiro Morizane, Asuka Ono, Yuichi Sekiguchi, Kiyotoshi Nakagawa, Masato Parmar, Malin Takahashi, Jun |
author_facet | Doi, Daisuke Samata, Bumpei Katsukawa, Mitsuko Kikuchi, Tetsuhiro Morizane, Asuka Ono, Yuichi Sekiguchi, Kiyotoshi Nakagawa, Masato Parmar, Malin Takahashi, Jun |
author_sort | Doi, Daisuke |
collection | PubMed |
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. |
format | Online Article Text |
id | pubmed-3964289 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-39642892014-03-26 Isolation of Human Induced Pluripotent Stem Cell-Derived Dopaminergic Progenitors by Cell Sorting for Successful Transplantation Doi, Daisuke Samata, Bumpei Katsukawa, Mitsuko Kikuchi, Tetsuhiro Morizane, Asuka Ono, Yuichi Sekiguchi, Kiyotoshi Nakagawa, Masato Parmar, Malin Takahashi, Jun Stem Cell Reports Article 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. Elsevier 2014-03-06 /pmc/articles/PMC3964289/ /pubmed/24672756 http://dx.doi.org/10.1016/j.stemcr.2014.01.013 Text en © 2014 The Authors http://creativecommons.org/licenses/by-nc-nd/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution-NonCommercial-No Derivative Works License, which permits non-commercial use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Article Doi, Daisuke Samata, Bumpei Katsukawa, Mitsuko Kikuchi, Tetsuhiro Morizane, Asuka Ono, Yuichi Sekiguchi, Kiyotoshi Nakagawa, Masato Parmar, Malin Takahashi, Jun Isolation of Human Induced Pluripotent Stem Cell-Derived Dopaminergic Progenitors by Cell Sorting for Successful Transplantation |
title | 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_short | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3964289/ https://www.ncbi.nlm.nih.gov/pubmed/24672756 http://dx.doi.org/10.1016/j.stemcr.2014.01.013 |
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