Luminescent Human iPSC-Derived Neurospheroids Enable Modeling of Neurotoxicity After Oxygen–glucose Deprivation
Abstract Despite the considerable impact of stroke on both the individual and on society, a neuroprotective therapy for stroke patients is missing. This is partially due to the current lack of a physiologically relevant human in vitro stroke model. To address this problem, we have developed a lumine...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Van Breedam, Elise [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2022 |
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| Schlagwörter: |
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| Anmerkung: |
© The American Society for Experimental NeuroTherapeutics, Inc. 2022. corrected publication 2022 |
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| Übergeordnetes Werk: |
Enthalten in: NeuroRX - Springer-Verlag, 2006, 19(2022), 2 vom: März, Seite 550-569 |
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| Übergeordnetes Werk: |
volume:19 ; year:2022 ; number:2 ; month:03 ; pages:550-569 |
| Links: |
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| DOI / URN: |
10.1007/s13311-022-01212-z |
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SPR047387025 |
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| 520 | |a Abstract Despite the considerable impact of stroke on both the individual and on society, a neuroprotective therapy for stroke patients is missing. This is partially due to the current lack of a physiologically relevant human in vitro stroke model. To address this problem, we have developed a luminescent human iPSC-derived neurospheroid model that enables real-time read-out of neural viability after ischemia-like conditions. We subjected 1- and 4-week-old neurospheroids, generated from iPSC-derived neural stem cells, to 6 h of oxygen–glucose deprivation (OGD) and measured neurospheroid luminescence. For both, we detected a decrease in luminescent signal due to ensuing neurotoxicity, as confirmed by conventional LDH assay and flow cytometric viability analysis. Remarkably, 1-week-old, but not 4-week-old neurospheroids recovered from OGD-induced injury, as evidenced by their reduced but overall increasing luminescence over time. This underscores the need for more mature neurospheroids, more faithfully recapitulating the in vivo situation. Furthermore, treatment of oxygen- and glucose-deprived neurospheroids with the pan-caspase inhibitor Z-VAD-FMK did not increase overall neural survival, despite its successful attenuation of apoptosis, in a human-based 3D environment. Nevertheless, owing to its three-dimensional organization and real-time viability reporting potential, the luminescent neurospheroids may become readily adopted in high-throughput screens aimed at identification of new therapeutic agents to treat acute ischemic stroke patients. | ||
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10.1007/s13311-022-01212-z doi (DE-627)SPR047387025 (SPR)s13311-022-01212-z-e DE-627 ger DE-627 rakwb eng Van Breedam, Elise verfasserin (orcid)0000-0002-7471-9064 aut Luminescent Human iPSC-Derived Neurospheroids Enable Modeling of Neurotoxicity After Oxygen–glucose Deprivation 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The American Society for Experimental NeuroTherapeutics, Inc. 2022. corrected publication 2022 Abstract Despite the considerable impact of stroke on both the individual and on society, a neuroprotective therapy for stroke patients is missing. This is partially due to the current lack of a physiologically relevant human in vitro stroke model. To address this problem, we have developed a luminescent human iPSC-derived neurospheroid model that enables real-time read-out of neural viability after ischemia-like conditions. We subjected 1- and 4-week-old neurospheroids, generated from iPSC-derived neural stem cells, to 6 h of oxygen–glucose deprivation (OGD) and measured neurospheroid luminescence. For both, we detected a decrease in luminescent signal due to ensuing neurotoxicity, as confirmed by conventional LDH assay and flow cytometric viability analysis. Remarkably, 1-week-old, but not 4-week-old neurospheroids recovered from OGD-induced injury, as evidenced by their reduced but overall increasing luminescence over time. This underscores the need for more mature neurospheroids, more faithfully recapitulating the in vivo situation. Furthermore, treatment of oxygen- and glucose-deprived neurospheroids with the pan-caspase inhibitor Z-VAD-FMK did not increase overall neural survival, despite its successful attenuation of apoptosis, in a human-based 3D environment. Nevertheless, owing to its three-dimensional organization and real-time viability reporting potential, the luminescent neurospheroids may become readily adopted in high-throughput screens aimed at identification of new therapeutic agents to treat acute ischemic stroke patients. iPSC (dpeaa)DE-He213 Neurospheroids (dpeaa)DE-He213 Oxygen–glucose deprivation (dpeaa)DE-He213 Bioluminescence (dpeaa)DE-He213 Neurotoxicity (dpeaa)DE-He213 Nijak, Aleksandra aut Buyle-Huybrecht, Tamariche (orcid)0000-0002-2123-8267 aut Di Stefano, Julia (orcid)0000-0003-3825-9803 aut Boeren, Marlies (orcid)0000-0002-7956-6730 aut Govaerts, Jonas (orcid)0000-0003-2688-3158 aut Quarta, Alessandra (orcid)0000-0002-7443-7104 aut Swartenbroekx, Tine aut Jacobs, Eva Z. aut Menten, Björn aut Gijsbers, Rik aut Delputte, Peter aut Alaerts, Maaike aut Hassannia, Behrouz aut Loeys, Bart aut Berneman, Zwi aut Timmermans, Jean-Pierre aut Jorens, Philippe G. aut Vanden Berghe, Tom aut Fransen, Erik aut Wouters, An aut De Vos, Winnok H. aut Ponsaerts, Peter (orcid)0000-0002-1892-6499 aut Enthalten in NeuroRX Springer-Verlag, 2006 19(2022), 2 vom: März, Seite 550-569 (DE-627)SPR031264964 nnns volume:19 year:2022 number:2 month:03 pages:550-569 https://dx.doi.org/10.1007/s13311-022-01212-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 19 2022 2 03 550-569 |
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10.1007/s13311-022-01212-z doi (DE-627)SPR047387025 (SPR)s13311-022-01212-z-e DE-627 ger DE-627 rakwb eng Van Breedam, Elise verfasserin (orcid)0000-0002-7471-9064 aut Luminescent Human iPSC-Derived Neurospheroids Enable Modeling of Neurotoxicity After Oxygen–glucose Deprivation 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The American Society for Experimental NeuroTherapeutics, Inc. 2022. corrected publication 2022 Abstract Despite the considerable impact of stroke on both the individual and on society, a neuroprotective therapy for stroke patients is missing. This is partially due to the current lack of a physiologically relevant human in vitro stroke model. To address this problem, we have developed a luminescent human iPSC-derived neurospheroid model that enables real-time read-out of neural viability after ischemia-like conditions. We subjected 1- and 4-week-old neurospheroids, generated from iPSC-derived neural stem cells, to 6 h of oxygen–glucose deprivation (OGD) and measured neurospheroid luminescence. For both, we detected a decrease in luminescent signal due to ensuing neurotoxicity, as confirmed by conventional LDH assay and flow cytometric viability analysis. Remarkably, 1-week-old, but not 4-week-old neurospheroids recovered from OGD-induced injury, as evidenced by their reduced but overall increasing luminescence over time. This underscores the need for more mature neurospheroids, more faithfully recapitulating the in vivo situation. Furthermore, treatment of oxygen- and glucose-deprived neurospheroids with the pan-caspase inhibitor Z-VAD-FMK did not increase overall neural survival, despite its successful attenuation of apoptosis, in a human-based 3D environment. Nevertheless, owing to its three-dimensional organization and real-time viability reporting potential, the luminescent neurospheroids may become readily adopted in high-throughput screens aimed at identification of new therapeutic agents to treat acute ischemic stroke patients. iPSC (dpeaa)DE-He213 Neurospheroids (dpeaa)DE-He213 Oxygen–glucose deprivation (dpeaa)DE-He213 Bioluminescence (dpeaa)DE-He213 Neurotoxicity (dpeaa)DE-He213 Nijak, Aleksandra aut Buyle-Huybrecht, Tamariche (orcid)0000-0002-2123-8267 aut Di Stefano, Julia (orcid)0000-0003-3825-9803 aut Boeren, Marlies (orcid)0000-0002-7956-6730 aut Govaerts, Jonas (orcid)0000-0003-2688-3158 aut Quarta, Alessandra (orcid)0000-0002-7443-7104 aut Swartenbroekx, Tine aut Jacobs, Eva Z. aut Menten, Björn aut Gijsbers, Rik aut Delputte, Peter aut Alaerts, Maaike aut Hassannia, Behrouz aut Loeys, Bart aut Berneman, Zwi aut Timmermans, Jean-Pierre aut Jorens, Philippe G. aut Vanden Berghe, Tom aut Fransen, Erik aut Wouters, An aut De Vos, Winnok H. aut Ponsaerts, Peter (orcid)0000-0002-1892-6499 aut Enthalten in NeuroRX Springer-Verlag, 2006 19(2022), 2 vom: März, Seite 550-569 (DE-627)SPR031264964 nnns volume:19 year:2022 number:2 month:03 pages:550-569 https://dx.doi.org/10.1007/s13311-022-01212-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 19 2022 2 03 550-569 |
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10.1007/s13311-022-01212-z doi (DE-627)SPR047387025 (SPR)s13311-022-01212-z-e DE-627 ger DE-627 rakwb eng Van Breedam, Elise verfasserin (orcid)0000-0002-7471-9064 aut Luminescent Human iPSC-Derived Neurospheroids Enable Modeling of Neurotoxicity After Oxygen–glucose Deprivation 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The American Society for Experimental NeuroTherapeutics, Inc. 2022. corrected publication 2022 Abstract Despite the considerable impact of stroke on both the individual and on society, a neuroprotective therapy for stroke patients is missing. This is partially due to the current lack of a physiologically relevant human in vitro stroke model. To address this problem, we have developed a luminescent human iPSC-derived neurospheroid model that enables real-time read-out of neural viability after ischemia-like conditions. We subjected 1- and 4-week-old neurospheroids, generated from iPSC-derived neural stem cells, to 6 h of oxygen–glucose deprivation (OGD) and measured neurospheroid luminescence. For both, we detected a decrease in luminescent signal due to ensuing neurotoxicity, as confirmed by conventional LDH assay and flow cytometric viability analysis. Remarkably, 1-week-old, but not 4-week-old neurospheroids recovered from OGD-induced injury, as evidenced by their reduced but overall increasing luminescence over time. This underscores the need for more mature neurospheroids, more faithfully recapitulating the in vivo situation. Furthermore, treatment of oxygen- and glucose-deprived neurospheroids with the pan-caspase inhibitor Z-VAD-FMK did not increase overall neural survival, despite its successful attenuation of apoptosis, in a human-based 3D environment. Nevertheless, owing to its three-dimensional organization and real-time viability reporting potential, the luminescent neurospheroids may become readily adopted in high-throughput screens aimed at identification of new therapeutic agents to treat acute ischemic stroke patients. iPSC (dpeaa)DE-He213 Neurospheroids (dpeaa)DE-He213 Oxygen–glucose deprivation (dpeaa)DE-He213 Bioluminescence (dpeaa)DE-He213 Neurotoxicity (dpeaa)DE-He213 Nijak, Aleksandra aut Buyle-Huybrecht, Tamariche (orcid)0000-0002-2123-8267 aut Di Stefano, Julia (orcid)0000-0003-3825-9803 aut Boeren, Marlies (orcid)0000-0002-7956-6730 aut Govaerts, Jonas (orcid)0000-0003-2688-3158 aut Quarta, Alessandra (orcid)0000-0002-7443-7104 aut Swartenbroekx, Tine aut Jacobs, Eva Z. aut Menten, Björn aut Gijsbers, Rik aut Delputte, Peter aut Alaerts, Maaike aut Hassannia, Behrouz aut Loeys, Bart aut Berneman, Zwi aut Timmermans, Jean-Pierre aut Jorens, Philippe G. aut Vanden Berghe, Tom aut Fransen, Erik aut Wouters, An aut De Vos, Winnok H. aut Ponsaerts, Peter (orcid)0000-0002-1892-6499 aut Enthalten in NeuroRX Springer-Verlag, 2006 19(2022), 2 vom: März, Seite 550-569 (DE-627)SPR031264964 nnns volume:19 year:2022 number:2 month:03 pages:550-569 https://dx.doi.org/10.1007/s13311-022-01212-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 19 2022 2 03 550-569 |
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10.1007/s13311-022-01212-z doi (DE-627)SPR047387025 (SPR)s13311-022-01212-z-e DE-627 ger DE-627 rakwb eng Van Breedam, Elise verfasserin (orcid)0000-0002-7471-9064 aut Luminescent Human iPSC-Derived Neurospheroids Enable Modeling of Neurotoxicity After Oxygen–glucose Deprivation 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The American Society for Experimental NeuroTherapeutics, Inc. 2022. corrected publication 2022 Abstract Despite the considerable impact of stroke on both the individual and on society, a neuroprotective therapy for stroke patients is missing. This is partially due to the current lack of a physiologically relevant human in vitro stroke model. To address this problem, we have developed a luminescent human iPSC-derived neurospheroid model that enables real-time read-out of neural viability after ischemia-like conditions. We subjected 1- and 4-week-old neurospheroids, generated from iPSC-derived neural stem cells, to 6 h of oxygen–glucose deprivation (OGD) and measured neurospheroid luminescence. For both, we detected a decrease in luminescent signal due to ensuing neurotoxicity, as confirmed by conventional LDH assay and flow cytometric viability analysis. Remarkably, 1-week-old, but not 4-week-old neurospheroids recovered from OGD-induced injury, as evidenced by their reduced but overall increasing luminescence over time. This underscores the need for more mature neurospheroids, more faithfully recapitulating the in vivo situation. Furthermore, treatment of oxygen- and glucose-deprived neurospheroids with the pan-caspase inhibitor Z-VAD-FMK did not increase overall neural survival, despite its successful attenuation of apoptosis, in a human-based 3D environment. Nevertheless, owing to its three-dimensional organization and real-time viability reporting potential, the luminescent neurospheroids may become readily adopted in high-throughput screens aimed at identification of new therapeutic agents to treat acute ischemic stroke patients. iPSC (dpeaa)DE-He213 Neurospheroids (dpeaa)DE-He213 Oxygen–glucose deprivation (dpeaa)DE-He213 Bioluminescence (dpeaa)DE-He213 Neurotoxicity (dpeaa)DE-He213 Nijak, Aleksandra aut Buyle-Huybrecht, Tamariche (orcid)0000-0002-2123-8267 aut Di Stefano, Julia (orcid)0000-0003-3825-9803 aut Boeren, Marlies (orcid)0000-0002-7956-6730 aut Govaerts, Jonas (orcid)0000-0003-2688-3158 aut Quarta, Alessandra (orcid)0000-0002-7443-7104 aut Swartenbroekx, Tine aut Jacobs, Eva Z. aut Menten, Björn aut Gijsbers, Rik aut Delputte, Peter aut Alaerts, Maaike aut Hassannia, Behrouz aut Loeys, Bart aut Berneman, Zwi aut Timmermans, Jean-Pierre aut Jorens, Philippe G. aut Vanden Berghe, Tom aut Fransen, Erik aut Wouters, An aut De Vos, Winnok H. aut Ponsaerts, Peter (orcid)0000-0002-1892-6499 aut Enthalten in NeuroRX Springer-Verlag, 2006 19(2022), 2 vom: März, Seite 550-569 (DE-627)SPR031264964 nnns volume:19 year:2022 number:2 month:03 pages:550-569 https://dx.doi.org/10.1007/s13311-022-01212-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 19 2022 2 03 550-569 |
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10.1007/s13311-022-01212-z doi (DE-627)SPR047387025 (SPR)s13311-022-01212-z-e DE-627 ger DE-627 rakwb eng Van Breedam, Elise verfasserin (orcid)0000-0002-7471-9064 aut Luminescent Human iPSC-Derived Neurospheroids Enable Modeling of Neurotoxicity After Oxygen–glucose Deprivation 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The American Society for Experimental NeuroTherapeutics, Inc. 2022. corrected publication 2022 Abstract Despite the considerable impact of stroke on both the individual and on society, a neuroprotective therapy for stroke patients is missing. This is partially due to the current lack of a physiologically relevant human in vitro stroke model. To address this problem, we have developed a luminescent human iPSC-derived neurospheroid model that enables real-time read-out of neural viability after ischemia-like conditions. We subjected 1- and 4-week-old neurospheroids, generated from iPSC-derived neural stem cells, to 6 h of oxygen–glucose deprivation (OGD) and measured neurospheroid luminescence. For both, we detected a decrease in luminescent signal due to ensuing neurotoxicity, as confirmed by conventional LDH assay and flow cytometric viability analysis. Remarkably, 1-week-old, but not 4-week-old neurospheroids recovered from OGD-induced injury, as evidenced by their reduced but overall increasing luminescence over time. This underscores the need for more mature neurospheroids, more faithfully recapitulating the in vivo situation. Furthermore, treatment of oxygen- and glucose-deprived neurospheroids with the pan-caspase inhibitor Z-VAD-FMK did not increase overall neural survival, despite its successful attenuation of apoptosis, in a human-based 3D environment. Nevertheless, owing to its three-dimensional organization and real-time viability reporting potential, the luminescent neurospheroids may become readily adopted in high-throughput screens aimed at identification of new therapeutic agents to treat acute ischemic stroke patients. iPSC (dpeaa)DE-He213 Neurospheroids (dpeaa)DE-He213 Oxygen–glucose deprivation (dpeaa)DE-He213 Bioluminescence (dpeaa)DE-He213 Neurotoxicity (dpeaa)DE-He213 Nijak, Aleksandra aut Buyle-Huybrecht, Tamariche (orcid)0000-0002-2123-8267 aut Di Stefano, Julia (orcid)0000-0003-3825-9803 aut Boeren, Marlies (orcid)0000-0002-7956-6730 aut Govaerts, Jonas (orcid)0000-0003-2688-3158 aut Quarta, Alessandra (orcid)0000-0002-7443-7104 aut Swartenbroekx, Tine aut Jacobs, Eva Z. aut Menten, Björn aut Gijsbers, Rik aut Delputte, Peter aut Alaerts, Maaike aut Hassannia, Behrouz aut Loeys, Bart aut Berneman, Zwi aut Timmermans, Jean-Pierre aut Jorens, Philippe G. aut Vanden Berghe, Tom aut Fransen, Erik aut Wouters, An aut De Vos, Winnok H. aut Ponsaerts, Peter (orcid)0000-0002-1892-6499 aut Enthalten in NeuroRX Springer-Verlag, 2006 19(2022), 2 vom: März, Seite 550-569 (DE-627)SPR031264964 nnns volume:19 year:2022 number:2 month:03 pages:550-569 https://dx.doi.org/10.1007/s13311-022-01212-z lizenzpflichtig Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER AR 19 2022 2 03 550-569 |
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Enthalten in NeuroRX 19(2022), 2 vom: März, Seite 550-569 volume:19 year:2022 number:2 month:03 pages:550-569 |
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Van Breedam, Elise @@aut@@ Nijak, Aleksandra @@aut@@ Buyle-Huybrecht, Tamariche @@aut@@ Di Stefano, Julia @@aut@@ Boeren, Marlies @@aut@@ Govaerts, Jonas @@aut@@ Quarta, Alessandra @@aut@@ Swartenbroekx, Tine @@aut@@ Jacobs, Eva Z. @@aut@@ Menten, Björn @@aut@@ Gijsbers, Rik @@aut@@ Delputte, Peter @@aut@@ Alaerts, Maaike @@aut@@ Hassannia, Behrouz @@aut@@ Loeys, Bart @@aut@@ Berneman, Zwi @@aut@@ Timmermans, Jean-Pierre @@aut@@ Jorens, Philippe G. @@aut@@ Vanden Berghe, Tom @@aut@@ Fransen, Erik @@aut@@ Wouters, An @@aut@@ De Vos, Winnok H. @@aut@@ Ponsaerts, Peter @@aut@@ |
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Van Breedam, Elise misc iPSC misc Neurospheroids misc Oxygen–glucose deprivation misc Bioluminescence misc Neurotoxicity Luminescent Human iPSC-Derived Neurospheroids Enable Modeling of Neurotoxicity After Oxygen–glucose Deprivation |
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Van Breedam, Elise Nijak, Aleksandra Buyle-Huybrecht, Tamariche Di Stefano, Julia Boeren, Marlies Govaerts, Jonas Quarta, Alessandra Swartenbroekx, Tine Jacobs, Eva Z. Menten, Björn Gijsbers, Rik Delputte, Peter Alaerts, Maaike Hassannia, Behrouz Loeys, Bart Berneman, Zwi Timmermans, Jean-Pierre Jorens, Philippe G. Vanden Berghe, Tom Fransen, Erik Wouters, An De Vos, Winnok H. Ponsaerts, Peter |
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luminescent human ipsc-derived neurospheroids enable modeling of neurotoxicity after oxygen–glucose deprivation |
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Luminescent Human iPSC-Derived Neurospheroids Enable Modeling of Neurotoxicity After Oxygen–glucose Deprivation |
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Abstract Despite the considerable impact of stroke on both the individual and on society, a neuroprotective therapy for stroke patients is missing. This is partially due to the current lack of a physiologically relevant human in vitro stroke model. To address this problem, we have developed a luminescent human iPSC-derived neurospheroid model that enables real-time read-out of neural viability after ischemia-like conditions. We subjected 1- and 4-week-old neurospheroids, generated from iPSC-derived neural stem cells, to 6 h of oxygen–glucose deprivation (OGD) and measured neurospheroid luminescence. For both, we detected a decrease in luminescent signal due to ensuing neurotoxicity, as confirmed by conventional LDH assay and flow cytometric viability analysis. Remarkably, 1-week-old, but not 4-week-old neurospheroids recovered from OGD-induced injury, as evidenced by their reduced but overall increasing luminescence over time. This underscores the need for more mature neurospheroids, more faithfully recapitulating the in vivo situation. Furthermore, treatment of oxygen- and glucose-deprived neurospheroids with the pan-caspase inhibitor Z-VAD-FMK did not increase overall neural survival, despite its successful attenuation of apoptosis, in a human-based 3D environment. Nevertheless, owing to its three-dimensional organization and real-time viability reporting potential, the luminescent neurospheroids may become readily adopted in high-throughput screens aimed at identification of new therapeutic agents to treat acute ischemic stroke patients. © The American Society for Experimental NeuroTherapeutics, Inc. 2022. corrected publication 2022 |
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Abstract Despite the considerable impact of stroke on both the individual and on society, a neuroprotective therapy for stroke patients is missing. This is partially due to the current lack of a physiologically relevant human in vitro stroke model. To address this problem, we have developed a luminescent human iPSC-derived neurospheroid model that enables real-time read-out of neural viability after ischemia-like conditions. We subjected 1- and 4-week-old neurospheroids, generated from iPSC-derived neural stem cells, to 6 h of oxygen–glucose deprivation (OGD) and measured neurospheroid luminescence. For both, we detected a decrease in luminescent signal due to ensuing neurotoxicity, as confirmed by conventional LDH assay and flow cytometric viability analysis. Remarkably, 1-week-old, but not 4-week-old neurospheroids recovered from OGD-induced injury, as evidenced by their reduced but overall increasing luminescence over time. This underscores the need for more mature neurospheroids, more faithfully recapitulating the in vivo situation. Furthermore, treatment of oxygen- and glucose-deprived neurospheroids with the pan-caspase inhibitor Z-VAD-FMK did not increase overall neural survival, despite its successful attenuation of apoptosis, in a human-based 3D environment. Nevertheless, owing to its three-dimensional organization and real-time viability reporting potential, the luminescent neurospheroids may become readily adopted in high-throughput screens aimed at identification of new therapeutic agents to treat acute ischemic stroke patients. © The American Society for Experimental NeuroTherapeutics, Inc. 2022. corrected publication 2022 |
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Abstract Despite the considerable impact of stroke on both the individual and on society, a neuroprotective therapy for stroke patients is missing. This is partially due to the current lack of a physiologically relevant human in vitro stroke model. To address this problem, we have developed a luminescent human iPSC-derived neurospheroid model that enables real-time read-out of neural viability after ischemia-like conditions. We subjected 1- and 4-week-old neurospheroids, generated from iPSC-derived neural stem cells, to 6 h of oxygen–glucose deprivation (OGD) and measured neurospheroid luminescence. For both, we detected a decrease in luminescent signal due to ensuing neurotoxicity, as confirmed by conventional LDH assay and flow cytometric viability analysis. Remarkably, 1-week-old, but not 4-week-old neurospheroids recovered from OGD-induced injury, as evidenced by their reduced but overall increasing luminescence over time. This underscores the need for more mature neurospheroids, more faithfully recapitulating the in vivo situation. Furthermore, treatment of oxygen- and glucose-deprived neurospheroids with the pan-caspase inhibitor Z-VAD-FMK did not increase overall neural survival, despite its successful attenuation of apoptosis, in a human-based 3D environment. Nevertheless, owing to its three-dimensional organization and real-time viability reporting potential, the luminescent neurospheroids may become readily adopted in high-throughput screens aimed at identification of new therapeutic agents to treat acute ischemic stroke patients. © The American Society for Experimental NeuroTherapeutics, Inc. 2022. corrected publication 2022 |
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