Skip to main content

Lund University Publications

LUND UNIVERSITY LIBRARIES

Robust derivation of transplantable dopamine neurons from human pluripotent stem cells by timed retinoic acid delivery

Alekseenko, Zhanna ; Dias, José M. ; Adler, Andrew LU ; Kozhevnikova, Mariya ; van Lunteren, Josina Anna ; Nolbrant, Sara LU ; Jeggari, Ashwini ; Vasylovska, Svitlana ; Yoshitake, Takashi and Kehr, Jan , et al. (2022) In Nature Communications 13.
Abstract
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... (More)
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. (Less)
Please use this url to cite or link to this publication:
author
; ; ; ; ; ; ; ; and , et al. (More)
; ; ; ; ; ; ; ; ; ; ; ; and (Less)
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
13
article number
3046 (2022)
publisher
Nature Publishing Group
external identifiers
  • pmid:35650213
  • scopus:85131145859
ISSN
2041-1723
DOI
10.1038/s41467-022-30777-8
language
English
LU publication?
yes
id
e9619b1d-eff4-49f0-ac7e-f3a5403995d5
date added to LUP
2022-06-02 14:59:23
date last changed
2024-02-18 03:05:23
@article{e9619b1d-eff4-49f0-ac7e-f3a5403995d5,
  abstract     = {{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.}},
  author       = {{Alekseenko, Zhanna and Dias, José M. and Adler, Andrew and Kozhevnikova, Mariya and van Lunteren, Josina Anna and Nolbrant, Sara and Jeggari, Ashwini and Vasylovska, Svitlana and Yoshitake, Takashi and Kehr, Jan and Carlén, Marie and Alexeyenko, Andrey and Parmar, Malin and Ericson, Johan}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  month        = {{06}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Robust derivation of transplantable dopamine neurons from human pluripotent stem cells by timed retinoic acid delivery}},
  url          = {{http://dx.doi.org/10.1038/s41467-022-30777-8}},
  doi          = {{10.1038/s41467-022-30777-8}},
  volume       = {{13}},
  year         = {{2022}},
}