Nanotherapeutic Modulation of Human Neural Cells and Glioblastoma in Organoids and Monocultures
Inflammatory processes in the brain are orchestrated by microglia and astrocytes in response to activators such as pathogen-associated molecular patterns, danger-associated molecular patterns and some nanostructures. Microglia are the primary immune responders in the brain and initiate responses amp...
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MDPI AG
2020-11-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/11/2434 |
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| author | Issan Zhang Paula Lépine Chanshuai Han María Lacalle-Aurioles Carol X.-Q. Chen Rainer Haag Thomas M. Durcan Dusica Maysinger |
| author_facet | Issan Zhang Paula Lépine Chanshuai Han María Lacalle-Aurioles Carol X.-Q. Chen Rainer Haag Thomas M. Durcan Dusica Maysinger |
| author_sort | Issan Zhang |
| collection | DOAJ |
| description | Inflammatory processes in the brain are orchestrated by microglia and astrocytes in response to activators such as pathogen-associated molecular patterns, danger-associated molecular patterns and some nanostructures. Microglia are the primary immune responders in the brain and initiate responses amplified by astrocytes through intercellular signaling. Intercellular communication between neural cells can be studied in cerebral organoids, co-cultures or in vivo. We used human cerebral organoids and glioblastoma co-cultures to study glia modulation by dendritic polyglycerol sulfate (dPGS). dPGS is an extensively studied nanostructure with inherent anti-inflammatory properties. Under inflammatory conditions, lipocalin-2 levels in astrocytes are markedly increased and indirectly enhanced by soluble factors released from hyperactive microglia. dPGS is an effective anti-inflammatory modulator of these markers. Our results show that dPGS can enter neural cells in cerebral organoids and glial cells in monocultures in a time-dependent manner. dPGS markedly reduces lipocalin-2 abundance in the neural cells. Glioblastoma tumoroids of astrocytic origin respond to activated microglia with enhanced invasiveness, whereas conditioned media from dPGS-treated microglia reduce tumoroid invasiveness. Considering that many nanostructures have only been tested in cancer cells and rodent models, experiments in human 3D cerebral organoids and co-cultures are complementary in vitro models to evaluate nanotherapeutics in the pre-clinical setting. Thoroughly characterized organoids and standardized procedures for their preparation are prerequisites to gain information of translational value in nanomedicine. This study provides data for a well-characterized dendrimer (dPGS) that modulates the activation state of human microglia implicated in brain tumor invasiveness. |
| first_indexed | 2024-03-10T15:00:31Z |
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| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T15:00:31Z |
| publishDate | 2020-11-01 |
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| record_format | Article |
| series | Cells |
| spelling | doaj.art-171cdaa0a0e84917b308b3e1aaf314262023-11-20T20:10:04ZengMDPI AGCells2073-44092020-11-01911243410.3390/cells9112434Nanotherapeutic Modulation of Human Neural Cells and Glioblastoma in Organoids and MonoculturesIssan Zhang0Paula Lépine1Chanshuai Han2María Lacalle-Aurioles3Carol X.-Q. Chen4Rainer Haag5Thomas M. Durcan6Dusica Maysinger7Department of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montreal, QC H3G 1Y6, CanadaThe Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, CanadaThe Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, CanadaThe Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, CanadaThe Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, CanadaInstitute of Chemistry and Biochemistry, Freie Universität Berlin, Takustraße 3, 14195 Berlin, GermanyThe Neuro’s Early Drug Discovery Unit (EDDU), McGill University, 3801 University Street, Montreal, QC H3A 2B4, CanadaDepartment of Pharmacology and Therapeutics, McGill University, 3655 Promenade Sir-William-Osler, Montreal, QC H3G 1Y6, CanadaInflammatory processes in the brain are orchestrated by microglia and astrocytes in response to activators such as pathogen-associated molecular patterns, danger-associated molecular patterns and some nanostructures. Microglia are the primary immune responders in the brain and initiate responses amplified by astrocytes through intercellular signaling. Intercellular communication between neural cells can be studied in cerebral organoids, co-cultures or in vivo. We used human cerebral organoids and glioblastoma co-cultures to study glia modulation by dendritic polyglycerol sulfate (dPGS). dPGS is an extensively studied nanostructure with inherent anti-inflammatory properties. Under inflammatory conditions, lipocalin-2 levels in astrocytes are markedly increased and indirectly enhanced by soluble factors released from hyperactive microglia. dPGS is an effective anti-inflammatory modulator of these markers. Our results show that dPGS can enter neural cells in cerebral organoids and glial cells in monocultures in a time-dependent manner. dPGS markedly reduces lipocalin-2 abundance in the neural cells. Glioblastoma tumoroids of astrocytic origin respond to activated microglia with enhanced invasiveness, whereas conditioned media from dPGS-treated microglia reduce tumoroid invasiveness. Considering that many nanostructures have only been tested in cancer cells and rodent models, experiments in human 3D cerebral organoids and co-cultures are complementary in vitro models to evaluate nanotherapeutics in the pre-clinical setting. Thoroughly characterized organoids and standardized procedures for their preparation are prerequisites to gain information of translational value in nanomedicine. This study provides data for a well-characterized dendrimer (dPGS) that modulates the activation state of human microglia implicated in brain tumor invasiveness.https://www.mdpi.com/2073-4409/9/11/2434cerebral organoidsnanomedicinesastrocytesmicrogliaglioblastomalipocalin-2 |
| spellingShingle | Issan Zhang Paula Lépine Chanshuai Han María Lacalle-Aurioles Carol X.-Q. Chen Rainer Haag Thomas M. Durcan Dusica Maysinger Nanotherapeutic Modulation of Human Neural Cells and Glioblastoma in Organoids and Monocultures Cells cerebral organoids nanomedicines astrocytes microglia glioblastoma lipocalin-2 |
| title | Nanotherapeutic Modulation of Human Neural Cells and Glioblastoma in Organoids and Monocultures |
| title_full | Nanotherapeutic Modulation of Human Neural Cells and Glioblastoma in Organoids and Monocultures |
| title_fullStr | Nanotherapeutic Modulation of Human Neural Cells and Glioblastoma in Organoids and Monocultures |
| title_full_unstemmed | Nanotherapeutic Modulation of Human Neural Cells and Glioblastoma in Organoids and Monocultures |
| title_short | Nanotherapeutic Modulation of Human Neural Cells and Glioblastoma in Organoids and Monocultures |
| title_sort | nanotherapeutic modulation of human neural cells and glioblastoma in organoids and monocultures |
| topic | cerebral organoids nanomedicines astrocytes microglia glioblastoma lipocalin-2 |
| url | https://www.mdpi.com/2073-4409/9/11/2434 |
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