Journal Article

DZNE-2020-03076

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Differentiation of chromaffin progenitor cells to dopaminergic neurons.

Vukicevic, V. ; Schmid, J. ; Hermann, A. ; Lange, S. ; Qin, N. ; Gebauer, L. ; Chunk, K.-F. ; Ravens, U. ; Eisenhofer, G. ; Storch, A.DZNE* ; Ader, M. ; Bornstein, S. R. ; Ehrhart-Bornstein, M. (Corresponding author)

2012
SAGE Publishing Thousand Oaks, CA

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Please use a persistent id in citations: doi:10.3727/096368912X638874

Abstract: The differentiation of dopamine-producing neurons from chromaffin progenitors might represent a new valuable source for replacement therapies in Parkinson's disease. However, characterization of their differentiation potential is an important prerequisite for efficient engraftment. Based on our previous studies on isolation and characterization of chromaffin progenitors from adult adrenals, this study investigates their potential to produce dopaminergic neurons and means to enhance their dopaminergic differentiation. Chromaffin progenitors grown in sphere culture showed an increased expression of nestin and Mash1, indicating an increase of the progenitor subset. Proneurogenic culture conditions induced the differentiation into neurons positive for neural markers β-III-tubulin, MAP2, and TH accompanied by a decrease of Mash1 and nestin. Furthermore, Notch2 expression decreased concomitantly with a downregulation of downstream effectors Hes1 and Hes5 responsible for self-renewal and proliferation maintenance of progenitor cells. Chromaffin progenitor-derived neurons secreted dopamine upon stimulation by potassium. Strikingly, treatment of differentiating cells with retinoic and ascorbic acid resulted in a twofold increase of dopamine secretion while norepinephrine and epinephrine were decreased. Initiation of dopamine synthesis and neural maturation is controlled by Pitx3 and Nurr1. Both Pitx3 and Nurr1 were identified in differentiating chromaffin progenitors. Along with the gained dopaminergic function, electrophysiology revealed features of mature neurons, such as sodium channels and the capability to fire multiple action potentials. In summary, this study elucidates the capacity of chromaffin progenitor cells to generate functional dopaminergic neurons, indicating their potential use in cell replacement therapies.

Keyword(s): Animals (MeSH) ; Cattle (MeSH) ; Cell Differentiation: physiology (MeSH) ; Cell Proliferation (MeSH) ; Cells, Cultured (MeSH) ; Chromaffin Cells: cytology (MeSH) ; Chromaffin Cells: metabolism (MeSH) ; Dopaminergic Neurons: cytology (MeSH) ; Dopaminergic Neurons: metabolism (MeSH) ; Stem Cells: cytology (MeSH) ; Stem Cells: metabolism (MeSH) ; Tretinoin: metabolism (MeSH) ; Tretinoin

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Contributing Institute(s):

1. Non-Motor Symptoms in Parkinson's disease (AG Storch)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2012

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