Preclinical Studies with Glioblastoma Brain Organoid Co-Cultures Show Efficient 5-ALA Photodynamic Therapy
Background: The high recurrence of glioblastoma (GB) that occurs adjacent to the resection cavity within two years of diagnosis urges an improvement of therapies oriented to GB local control. Photodynamic therapy (PDT) has been proposed to cleanse infiltrating tumor cells from parenchyma to ameliora...
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MDPI AG
2023-04-01
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| Series: | Cells |
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| Online Access: | https://www.mdpi.com/2073-4409/12/8/1125 |
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| author | Leire Pedrosa Carmen Bedia Diouldé Diao Alejandra Mosteiro Abel Ferrés Elisabetta Stanzani Fina Martínez-Soler Avelina Tortosa Estela Pineda Iban Aldecoa Marc Centellas Marta Muñoz-Tudurí Ana Sevilla Àngels Sierra José Juan González Sánchez |
| author_facet | Leire Pedrosa Carmen Bedia Diouldé Diao Alejandra Mosteiro Abel Ferrés Elisabetta Stanzani Fina Martínez-Soler Avelina Tortosa Estela Pineda Iban Aldecoa Marc Centellas Marta Muñoz-Tudurí Ana Sevilla Àngels Sierra José Juan González Sánchez |
| author_sort | Leire Pedrosa |
| collection | DOAJ |
| description | Background: The high recurrence of glioblastoma (GB) that occurs adjacent to the resection cavity within two years of diagnosis urges an improvement of therapies oriented to GB local control. Photodynamic therapy (PDT) has been proposed to cleanse infiltrating tumor cells from parenchyma to ameliorate short long-term progression-free survival. We examined 5-aminolevulinic acid (5-ALA)-mediated PDT effects as therapeutical treatment and determined optimal conditions for PDT efficacy without causing phototoxic injury to the normal brain tissue. Methods: We used a platform of Glioma Initiation Cells (GICs) infiltrating cerebral organoids with two different glioblastoma cells, GIC7 and PG88. We measured GICs-5-ALA uptake and PDT/5-ALA activity in dose-response curves and the efficacy of the treatment by measuring proliferative activity and apoptosis. Results: 5-ALA (50 and 100 µg/mL) was applied, and the release of protoporphyrin IX (<i>PpIX</i>) fluorescence measures demonstrated that the emission of <i>PpIX</i> increases progressively until its stabilization at 24 h. Moreover, decreased proliferation and increased apoptosis corroborated the effect of 5-ALA/PDT on cancer cells without altering normal cells. Conclusions: We provide evidence about the effectiveness of PDT to treat high proliferative GB cells in a complex in vitro system, which combines normal and cancer cells and is a useful tool to standardize new strategic therapies. |
| first_indexed | 2024-03-11T05:08:53Z |
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| id | doaj.art-3f9a3843afdf41a58fc5dbaf0da3fe5a |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-11T05:08:53Z |
| publishDate | 2023-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-3f9a3843afdf41a58fc5dbaf0da3fe5a2023-11-17T18:42:52ZengMDPI AGCells2073-44092023-04-01128112510.3390/cells12081125Preclinical Studies with Glioblastoma Brain Organoid Co-Cultures Show Efficient 5-ALA Photodynamic TherapyLeire Pedrosa0Carmen Bedia1Diouldé Diao2Alejandra Mosteiro3Abel Ferrés4Elisabetta Stanzani5Fina Martínez-Soler6Avelina Tortosa7Estela Pineda8Iban Aldecoa9Marc Centellas10Marta Muñoz-Tudurí11Ana Sevilla12Àngels Sierra13José Juan González Sánchez14Laboratory of Experimental Oncological Neurosurgery, Neurosurgery Service, Hospital Clinic de Barcelona—FCRB, 08036 Barcelona, SpainInstitute of Environmental Assessment and Water Research (IDAEA-CSIC), 08034 Barcelona, SpainLaboratory of Experimental Oncological Neurosurgery, Neurosurgery Service, Hospital Clinic de Barcelona—FCRB, 08036 Barcelona, SpainDepartment of Neurosurgery, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, SpainDepartment of Neurosurgery, Hospital Clínic de Barcelona, University of Barcelona, 08036 Barcelona, SpainLaboratory of Pharmacology and Brain Pathology, IRCCS Humanitas Research Hospital, 20089 Milan, ItalyApoptosis and Cancer Unit, Department of Basic Nursing, IDIBELL, Faculty of Medicine and Health Sciences, University of Barcelona, 08907 L’Hospitalet del Llobregat, SpainApoptosis and Cancer Unit, Department of Basic Nursing, IDIBELL, Faculty of Medicine and Health Sciences, University of Barcelona, 08907 L’Hospitalet del Llobregat, SpainMedical Oncology Department, Hospital Clinic and Translational Genomics and Targeted Therapies in Solid Tumors, IDIBAPS, 08036 Barcelona, SpainDepartment of Pathology, Biomedical Diagnostic Center, Hospital Clínic of Barcelona, University of Barcelona, 08036 Barcelona, SpainLaboratorios Gebro Pharma S.A., 08022 Barcelona, SpainLaboratorios Gebro Pharma S.A., 08022 Barcelona, SpainDepartment of Cell Biology, Physiology and Immunology, Faculty of Biology, University of Barcelona, 08028 Barcelona, SpainLaboratory of Experimental Oncological Neurosurgery, Neurosurgery Service, Hospital Clinic de Barcelona—FCRB, 08036 Barcelona, SpainLaboratory of Experimental Oncological Neurosurgery, Neurosurgery Service, Hospital Clinic de Barcelona—FCRB, 08036 Barcelona, SpainBackground: The high recurrence of glioblastoma (GB) that occurs adjacent to the resection cavity within two years of diagnosis urges an improvement of therapies oriented to GB local control. Photodynamic therapy (PDT) has been proposed to cleanse infiltrating tumor cells from parenchyma to ameliorate short long-term progression-free survival. We examined 5-aminolevulinic acid (5-ALA)-mediated PDT effects as therapeutical treatment and determined optimal conditions for PDT efficacy without causing phototoxic injury to the normal brain tissue. Methods: We used a platform of Glioma Initiation Cells (GICs) infiltrating cerebral organoids with two different glioblastoma cells, GIC7 and PG88. We measured GICs-5-ALA uptake and PDT/5-ALA activity in dose-response curves and the efficacy of the treatment by measuring proliferative activity and apoptosis. Results: 5-ALA (50 and 100 µg/mL) was applied, and the release of protoporphyrin IX (<i>PpIX</i>) fluorescence measures demonstrated that the emission of <i>PpIX</i> increases progressively until its stabilization at 24 h. Moreover, decreased proliferation and increased apoptosis corroborated the effect of 5-ALA/PDT on cancer cells without altering normal cells. Conclusions: We provide evidence about the effectiveness of PDT to treat high proliferative GB cells in a complex in vitro system, which combines normal and cancer cells and is a useful tool to standardize new strategic therapies.https://www.mdpi.com/2073-4409/12/8/11255-ALA3D tumor modelsneurological cancersdrug screeningglioblastomaorganoids |
| spellingShingle | Leire Pedrosa Carmen Bedia Diouldé Diao Alejandra Mosteiro Abel Ferrés Elisabetta Stanzani Fina Martínez-Soler Avelina Tortosa Estela Pineda Iban Aldecoa Marc Centellas Marta Muñoz-Tudurí Ana Sevilla Àngels Sierra José Juan González Sánchez Preclinical Studies with Glioblastoma Brain Organoid Co-Cultures Show Efficient 5-ALA Photodynamic Therapy Cells 5-ALA 3D tumor models neurological cancers drug screening glioblastoma organoids |
| title | Preclinical Studies with Glioblastoma Brain Organoid Co-Cultures Show Efficient 5-ALA Photodynamic Therapy |
| title_full | Preclinical Studies with Glioblastoma Brain Organoid Co-Cultures Show Efficient 5-ALA Photodynamic Therapy |
| title_fullStr | Preclinical Studies with Glioblastoma Brain Organoid Co-Cultures Show Efficient 5-ALA Photodynamic Therapy |
| title_full_unstemmed | Preclinical Studies with Glioblastoma Brain Organoid Co-Cultures Show Efficient 5-ALA Photodynamic Therapy |
| title_short | Preclinical Studies with Glioblastoma Brain Organoid Co-Cultures Show Efficient 5-ALA Photodynamic Therapy |
| title_sort | preclinical studies with glioblastoma brain organoid co cultures show efficient 5 ala photodynamic therapy |
| topic | 5-ALA 3D tumor models neurological cancers drug screening glioblastoma organoids |
| url | https://www.mdpi.com/2073-4409/12/8/1125 |
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