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

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 pro

SUBMITTER: Alekseenko Z 

PROVIDER: S-EPMC9160024 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature