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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 LU ; Ono, Yuichi; Sekiguchi, Kiyotoshi; Nakagawa, Masato; Parmar, Malin LU and Takahashi, Jun (2014) In Stem Cell Reports 2(3). p.337-350
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Stem Cell Reports
volume
2
issue
3
pages
337 - 350
publisher
Cell Press
external identifiers
  • pmid:24672756
  • wos:000336647700009
  • scopus:84896084435
ISSN
2213-6711
DOI
10.1016/j.stemcr.2014.01.013
language
English
LU publication?
yes
id
3a792abe-e9d7-485f-840f-be252c9d52d1 (old id 4379606)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/24672756?dopt=Abstract
date added to LUP
2014-04-04 20:20:51
date last changed
2017-10-22 04:23:52
@article{3a792abe-e9d7-485f-840f-be252c9d52d1,
  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.},
  author       = {Doi, Daisuke and Samata, Bumpei and Katsukawa, Mitsuko and Kikuchi, Tetsuhiro and Morizane, Asuka and Ono, Yuichi and Sekiguchi, Kiyotoshi and Nakagawa, Masato and Parmar, Malin and Takahashi, Jun},
  issn         = {2213-6711},
  language     = {eng},
  number       = {3},
  pages        = {337--350},
  publisher    = {Cell Press},
  series       = {Stem Cell Reports},
  title        = {Isolation of human induced pluripotent stem cell-derived dopaminergic progenitors by cell sorting for successful transplantation.},
  url          = {http://dx.doi.org/10.1016/j.stemcr.2014.01.013},
  volume       = {2},
  year         = {2014},
}