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Robust derivation o...
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Alekseenko, ZhannaKarolinska Institutet
(author)
Robust derivation of transplantable dopamine neurons from human pluripotent stem cells by timed retinoic acid delivery
- Article/chapterEnglish2022
Publisher, publication year, extent ...
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2022-06-01
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Springer Science and Business Media LLC,2022
Numbers
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LIBRIS-ID:oai:lup.lub.lu.se:e9619b1d-eff4-49f0-ac7e-f3a5403995d5
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https://lup.lub.lu.se/record/e9619b1d-eff4-49f0-ac7e-f3a5403995d5URI
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https://doi.org/10.1038/s41467-022-30777-8DOI
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http://kipublications.ki.se/Default.aspx?queryparsed=id:149730862URI
Supplementary language notes
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Language:English
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Summary in:English
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Subject category:art swepub-publicationtype
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Subject category:ref swepub-contenttype
Notes
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Stem cell therapies for Parkinson’s disease (PD) have entered first-in-human clinical trials using a set of technically related methods to produce mesencephalic dopamine (mDA) neurons from human pluripotent stem cells (hPSCs). Here, we outline an approach for high-yield derivation of mDA neurons that principally differs from alternative technologies by utilizing retinoic acid (RA) signaling, instead of WNT and FGF8 signaling, to specify mesencephalic fate. Unlike most morphogen signals, where precise concentration determines cell fate, it is the duration of RA exposure that is the key-parameter for mesencephalic specification. This concentration-insensitive patterning approach provides robustness and reduces the need for protocol-adjustments between hPSC-lines. RA-specified progenitors promptly differentiate into functional mDA neurons in vitro, and successfully engraft and relieve motor deficits after transplantation in a rat PD model. Our study provides a potential alternative route for cell therapy and disease modelling that due to its robustness could be particularly expedient when use of autologous- or immunologically matched cells is considered.
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Dias, José M.Karolinska Institutet
(author)
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Adler, AndrewLund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups(Swepub:lu)an8152ad
(author)
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Kozhevnikova, MariyaKarolinska Institutet
(author)
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van Lunteren, Josina AnnaKarolinska Institutet
(author)
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Nolbrant, SaraLund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups(Swepub:lu)med-sn2
(author)
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Jeggari, AshwiniKarolinska Institutet
(author)
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Vasylovska, SvitlanaKarolinska Institutet
(author)
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Yoshitake, TakashiKarolinska Institutet
(author)
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Kehr, JanKarolinska Institutet
(author)
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Carlén, MarieKarolinska Institutet
(author)
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Alexeyenko, AndreyKarolinska Institutet,Science for Life Laboratory (SciLifeLab)
(author)
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Parmar, MalinLund University,Lunds universitet,Utvecklings- och regenerativ neurobiologi,Forskargrupper vid Lunds universitet,Developmental and Regenerative Neurobiology,Lund University Research Groups(Swepub:lu)mphy-mpa
(author)
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Ericson, JohanKarolinska Institutet
(author)
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Karolinska InstitutetUtvecklings- och regenerativ neurobiologi
(creator_code:org_t)
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In:Nature Communications: Springer Science and Business Media LLC132041-1723
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Alekseenko, Zhan ...
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Dias, José M.
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Adler, Andrew
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van Lunteren, Jo ...
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Nolbrant, Sara
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Jeggari, Ashwini
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Kehr, Jan
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Carlén, Marie
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Parmar, Malin
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Ericson, Johan
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- MEDICAL AND HEALTH SCIENCES
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