Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells

Anna S. Monzel; Lisa M. Smits; Kathrin Hemmer; Siham Hachi; Edinson Lucumi Moreno; Thea van Wuellen; Javier Jarazo; Jonas Walter; Inga Brüggemann; Ibrahim Boussaad; Emanuel Berger; Ronan M.T. Fleming; Silvia Bolognin; Jens C. Schwamborn

doi:10.1016/j.stemcr.2017.03.010

Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells

Anna S. Monzel, Lisa M. Smits, Kathrin Hemmer, Siham Hachi, Edinson Lucumi Moreno, Thea van Wuellen, Javier Jarazo, Jonas Walter, Inga Brüggemann, Ibrahim Boussaad, Emanuel Berger, Ronan M.T. Fleming, Silvia Bolognin, Jens C. Schwamborn^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

306 Citations (Scopus)

Abstract

Research on human brain development and neurological diseases is limited by the lack of advanced experimental in vitro models that truly recapitulate the complexity of the human brain. Here, we describe a robust human brain organoid system that is highly specific to the midbrain derived from regionally patterned neuroepithelial stem cells. These human midbrain organoids contain spatially organized groups of dopaminergic neurons, which make them an attractive model for the study of Parkinson's disease. Midbrain organoids are characterized in detail for neuronal, astroglial, and oligodendrocyte differentiation. Furthermore, we show the presence of synaptic connections and electrophysiological activity. The complexity of this model is further highlighted by the myelination of neurites. The present midbrain organoid system has the potential to be used for advanced in vitro disease modeling and therapy development.

Original language	English
Pages (from-to)	1144-1154
Number of pages	11
Journal	Stem Cell Reports
Volume	8
Issue number	5
DOIs	https://doi.org/10.1016/j.stemcr.2017.03.010
Publication status	Published - 9 May 2017
Externally published	Yes

Keywords

midbrain
neural stem cells
organoid
Parkinson's disease
stem cells

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10.1016/j.stemcr.2017.03.010

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Monzel, A. S., Smits, L. M., Hemmer, K., Hachi, S., Moreno, E. L., van Wuellen, T., Jarazo, J., Walter, J., Brüggemann, I., Boussaad, I., Berger, E., Fleming, R. M. T., Bolognin, S., & Schwamborn, J. C. (2017). Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells. Stem Cell Reports, 8(5), 1144-1154. https://doi.org/10.1016/j.stemcr.2017.03.010

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abstract = "Research on human brain development and neurological diseases is limited by the lack of advanced experimental in vitro models that truly recapitulate the complexity of the human brain. Here, we describe a robust human brain organoid system that is highly specific to the midbrain derived from regionally patterned neuroepithelial stem cells. These human midbrain organoids contain spatially organized groups of dopaminergic neurons, which make them an attractive model for the study of Parkinson's disease. Midbrain organoids are characterized in detail for neuronal, astroglial, and oligodendrocyte differentiation. Furthermore, we show the presence of synaptic connections and electrophysiological activity. The complexity of this model is further highlighted by the myelination of neurites. The present midbrain organoid system has the potential to be used for advanced in vitro disease modeling and therapy development.",

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AU - Monzel, Anna S.

AU - Smits, Lisa M.

AU - Hemmer, Kathrin

AU - Hachi, Siham

AU - Moreno, Edinson Lucumi

AU - van Wuellen, Thea

AU - Jarazo, Javier

AU - Walter, Jonas

AU - Brüggemann, Inga

AU - Boussaad, Ibrahim

AU - Berger, Emanuel

AU - Fleming, Ronan M.T.

AU - Bolognin, Silvia

AU - Schwamborn, Jens C.

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AB - Research on human brain development and neurological diseases is limited by the lack of advanced experimental in vitro models that truly recapitulate the complexity of the human brain. Here, we describe a robust human brain organoid system that is highly specific to the midbrain derived from regionally patterned neuroepithelial stem cells. These human midbrain organoids contain spatially organized groups of dopaminergic neurons, which make them an attractive model for the study of Parkinson's disease. Midbrain organoids are characterized in detail for neuronal, astroglial, and oligodendrocyte differentiation. Furthermore, we show the presence of synaptic connections and electrophysiological activity. The complexity of this model is further highlighted by the myelination of neurites. The present midbrain organoid system has the potential to be used for advanced in vitro disease modeling and therapy development.

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Derivation of Human Midbrain-Specific Organoids from Neuroepithelial Stem Cells

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