TY - JOUR
T1 - Reproducible generation of human midbrain organoids for in vitro modeling of Parkinson's disease
AU - Nickels, Sarah Louise
AU - Modamio, Jennifer
AU - Mendes-Pinheiro, Bárbara
AU - Monzel, Anna Sophia
AU - Betsou, Fay
AU - Schwamborn, Jens Christian
N1 - Funding Information:
The authors thank Prof. Dr. Hans R. Sch?ler from the Max-Planck-Gesellschaft, Prof. Dr. Thomas Gasser from the Universitatsklinikum Tuebingen, and Dr. Jared Sterneckert from the CRTD for providing us with cell lines. Moreover, we thank Paul Anthony and Silvia Bolognin for setting up the scripts used for quantifying the immunocytochemistry and Javier Jarazo for deriving one of the cell lines. The JCS lab is supported by a Proof-of-Concept grant from the Fonds National de la Recherche (FNR) Luxembourg (FNR/PoC16/11559169). Further, this is an EU Joint Program ? Neurodegenerative Disease Research (JPND) project with FNR support (INTER/JPND/15/11092422). The JCS lab is additionally supported by the FET Proactive CONNECT project (Grant No. 824070). ASM was supported by a fellowship from the FNR (AFR, Aides ? la Formation- Recherche) and received support from the Lush prize 2017. BP was supported by the doctoral fellowship from Funda??o para a Ci?ncia e Tecnologia (SFRH/BD/120124/2016). Finally, the authors also thank the private donors who support the work at the Luxembourg Centre for Systems Biomedicine. JCS is co-founder and shareholder of the biotech company OrganoTherapeutics SARL.
Funding Information:
The JCS lab is supported by a Proof-of-Concept grant from the Fonds National de la Recherche (FNR) Luxembourg (FNR/PoC16/11559169). Further, this is an EU Joint Program – Neurodegenerative Disease Research (JPND) project with FNR support (INTER/JPND/15/11092422). The JCS lab is additionally supported by the FET Proactive CONNECT project (Grant No. 824070 ). ASM was supported by a fellowship from the FNR (AFR, Aides à la Formation- Recherche) and received support from the Lush prize 2017. BP was supported by the doctoral fellowship from Fundação para a Ciência e Tecnologia ( SFRH/BD/120124/2016 ). Finally, the authors also thank the private donors who support the work at the Luxembourg Centre for Systems Biomedicine.
Publisher Copyright:
© 2020 The Authors
PY - 2020/7
Y1 - 2020/7
N2 - The study of human midbrain development and midbrain related diseases, like Parkinson's disease (PD), is limited by deficiencies in the currently available and validated laboratory models. Three dimensional midbrain organoids represent an innovative strategy to recapitulate some aspects of the complexity and physiology of the human midbrain. Nevertheless, also these novel organoid models exhibit some inherent weaknesses, including the presence of a necrotic core and batch-to-batch variability. Here we describe an optimized approach for the standardized generation of midbrain organoids that addresses these limitations, while maintaining key features of midbrain development like dopaminergic neuron and astrocyte differentiation. Moreover, we have established a novel time-efficient, fit for purpose analysis pipeline and provided proof of concept for its usage by investigating toxin induced PD.
AB - The study of human midbrain development and midbrain related diseases, like Parkinson's disease (PD), is limited by deficiencies in the currently available and validated laboratory models. Three dimensional midbrain organoids represent an innovative strategy to recapitulate some aspects of the complexity and physiology of the human midbrain. Nevertheless, also these novel organoid models exhibit some inherent weaknesses, including the presence of a necrotic core and batch-to-batch variability. Here we describe an optimized approach for the standardized generation of midbrain organoids that addresses these limitations, while maintaining key features of midbrain development like dopaminergic neuron and astrocyte differentiation. Moreover, we have established a novel time-efficient, fit for purpose analysis pipeline and provided proof of concept for its usage by investigating toxin induced PD.
KW - Brain organoid
KW - Midbrain
KW - Parkinson's disease
KW - Standardization
KW - in vitro disease modeling
UR - http://www.scopus.com/inward/record.url?scp=85086133644&partnerID=8YFLogxK
U2 - 10.1016/j.scr.2020.101870
DO - 10.1016/j.scr.2020.101870
M3 - Article
C2 - 32534166
AN - SCOPUS:85086133644
SN - 1873-5061
VL - 46
JO - Stem Cell Research
JF - Stem Cell Research
M1 - 101870
ER -