Unraveling the assembloid: Real-time monitoring of dopaminergic neurites in an inter-organoid pathway connecting midbrain and striatal regions
Modern in vitro technologies for preclinical research, including organ-on-a-chip, organoids- and assembloid-based systems, have rapidly emerged as pivotal tools for elucidating disease mechanisms and assessing the efficacy of putative therapeutics. In this context, advanced in vitro models of Parkin...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-04-01
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| Series: | Materials Today Bio |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2590006424000516 |
| _version_ | 1797258685107404800 |
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| author | Alp Ozgun David J. Lomboni Amy Aylsworth Allison Macdonald William A. Staines Marzia Martina Michael G. Schlossmacher Joseph S. Tauskela John Woulfe Fabio Variola |
| author_facet | Alp Ozgun David J. Lomboni Amy Aylsworth Allison Macdonald William A. Staines Marzia Martina Michael G. Schlossmacher Joseph S. Tauskela John Woulfe Fabio Variola |
| author_sort | Alp Ozgun |
| collection | DOAJ |
| description | Modern in vitro technologies for preclinical research, including organ-on-a-chip, organoids- and assembloid-based systems, have rapidly emerged as pivotal tools for elucidating disease mechanisms and assessing the efficacy of putative therapeutics. In this context, advanced in vitro models of Parkinson's Disease (PD) offer the potential to accelerate drug discovery by enabling effective platforms that recapitulate both physiological and pathological attributes of the in vivo environment. Although these systems often aim at replicating the PD-associated loss of dopaminergic (DA) neurons, only a few have modelled the degradation of dopaminergic pathways as a way to mimic the disruption of downstream regulation mechanisms that define the characteristic motor symptoms of the disease. To this end, assembloids have been successfully employed to recapitulate neuronal pathways between distinct brain regions. However, the investigation and characterization of these connections through neural tracing and electrophysiological analysis remain a technically challenging and time-consuming process. Here, we present a novel bioengineered platform consisting of surface-grown midbrain and striatal organoids at opposite sides of a self-assembled DA pathway. In particular, dopaminergic neurons and striatal GABAergic neurons spontaneously form DA connections across a microelectrode array (MEA), specifically integrated for the real-time monitoring of electrophysiological development and stimuli response. Calcium imaging data showed spiking synchronicity of the two organoids forming the inter-organoid pathways (IOPs) demonstrating that they are functionally connected. MEA recordings confirm a more robust response to the DA neurotoxin 6-OHDA compared to midbrain organoids alone, thereby validating the potential of this technology to generate highly tractable, easily extractable real-time functional readouts to investigate the dysfunctional dopaminergic network of PD patients. |
| first_indexed | 2024-03-08T03:35:38Z |
| format | Article |
| id | doaj.art-d2bae2e1d0ce40cf9af33ace061c32c7 |
| institution | Directory Open Access Journal |
| issn | 2590-0064 |
| language | English |
| last_indexed | 2024-04-24T22:57:27Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Materials Today Bio |
| spelling | doaj.art-d2bae2e1d0ce40cf9af33ace061c32c72024-03-18T04:34:22ZengElsevierMaterials Today Bio2590-00642024-04-0125100992Unraveling the assembloid: Real-time monitoring of dopaminergic neurites in an inter-organoid pathway connecting midbrain and striatal regionsAlp Ozgun0David J. Lomboni1Amy Aylsworth2Allison Macdonald3William A. Staines4Marzia Martina5Michael G. Schlossmacher6Joseph S. Tauskela7John Woulfe8Fabio Variola9Department of Mechanical Engineering, Faculty of Engineering, University of Ottawa, Ottawa, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Canada; Program in Neuroscience, Ottawa Hospital Research Institute, Ottawa, CanadaDepartment of Mechanical Engineering, Faculty of Engineering, University of Ottawa, Ottawa, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, CanadaHuman Health Therapeutics Research Centre, National Research Council of Canada, Ottawa, CanadaDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Canada; Program in Neuroscience, Ottawa Hospital Research Institute, Ottawa, CanadaDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, CanadaHuman Health Therapeutics Research Centre, National Research Council of Canada, Ottawa, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, CanadaDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Canada; Program in Neuroscience, Ottawa Hospital Research Institute, Ottawa, Canada; University of Ottawa Brain and Mind Research Institute, Ottawa, Canada; Division of Neurology, Department of Medicine, The Ottawa Hospital, Ottawa, CanadaHuman Health Therapeutics Research Centre, National Research Council of Canada, Ottawa, CanadaDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Canada; Department of Pathology, The Ottawa Hospital, Ottawa, Canada; Corresponding author. Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Canada.Department of Mechanical Engineering, Faculty of Engineering, University of Ottawa, Ottawa, Canada; Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, Canada; Ottawa-Carleton Institute for Biomedical Engineering (OCIBME), Ottawa, Canada; Children's Hospital of Eastern Ontario (CHEO), Ottawa, Canada; Corresponding author. Department of Mechanical Engineering, Faculty of Engineering, University of Ottawa, Ottawa, Canada.Modern in vitro technologies for preclinical research, including organ-on-a-chip, organoids- and assembloid-based systems, have rapidly emerged as pivotal tools for elucidating disease mechanisms and assessing the efficacy of putative therapeutics. In this context, advanced in vitro models of Parkinson's Disease (PD) offer the potential to accelerate drug discovery by enabling effective platforms that recapitulate both physiological and pathological attributes of the in vivo environment. Although these systems often aim at replicating the PD-associated loss of dopaminergic (DA) neurons, only a few have modelled the degradation of dopaminergic pathways as a way to mimic the disruption of downstream regulation mechanisms that define the characteristic motor symptoms of the disease. To this end, assembloids have been successfully employed to recapitulate neuronal pathways between distinct brain regions. However, the investigation and characterization of these connections through neural tracing and electrophysiological analysis remain a technically challenging and time-consuming process. Here, we present a novel bioengineered platform consisting of surface-grown midbrain and striatal organoids at opposite sides of a self-assembled DA pathway. In particular, dopaminergic neurons and striatal GABAergic neurons spontaneously form DA connections across a microelectrode array (MEA), specifically integrated for the real-time monitoring of electrophysiological development and stimuli response. Calcium imaging data showed spiking synchronicity of the two organoids forming the inter-organoid pathways (IOPs) demonstrating that they are functionally connected. MEA recordings confirm a more robust response to the DA neurotoxin 6-OHDA compared to midbrain organoids alone, thereby validating the potential of this technology to generate highly tractable, easily extractable real-time functional readouts to investigate the dysfunctional dopaminergic network of PD patients.http://www.sciencedirect.com/science/article/pii/S2590006424000516 |
| spellingShingle | Alp Ozgun David J. Lomboni Amy Aylsworth Allison Macdonald William A. Staines Marzia Martina Michael G. Schlossmacher Joseph S. Tauskela John Woulfe Fabio Variola Unraveling the assembloid: Real-time monitoring of dopaminergic neurites in an inter-organoid pathway connecting midbrain and striatal regions Materials Today Bio |
| title | Unraveling the assembloid: Real-time monitoring of dopaminergic neurites in an inter-organoid pathway connecting midbrain and striatal regions |
| title_full | Unraveling the assembloid: Real-time monitoring of dopaminergic neurites in an inter-organoid pathway connecting midbrain and striatal regions |
| title_fullStr | Unraveling the assembloid: Real-time monitoring of dopaminergic neurites in an inter-organoid pathway connecting midbrain and striatal regions |
| title_full_unstemmed | Unraveling the assembloid: Real-time monitoring of dopaminergic neurites in an inter-organoid pathway connecting midbrain and striatal regions |
| title_short | Unraveling the assembloid: Real-time monitoring of dopaminergic neurites in an inter-organoid pathway connecting midbrain and striatal regions |
| title_sort | unraveling the assembloid real time monitoring of dopaminergic neurites in an inter organoid pathway connecting midbrain and striatal regions |
| url | http://www.sciencedirect.com/science/article/pii/S2590006424000516 |
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