Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Pedrosa, Leire, Bedia, Carmen, Diao, Diouldé, Mosteiro, Alejandra, Ferrés, Abel, Stanzani, Elisabetta, Martínez-Soler, Fina, Tortosa, Avelina, Pineda, Estela, Aldecoa, Iban, Centellas, Marc, Muñoz-Tudurí, Marta, Sevilla, Ana, Sierra, Àngels, González Sánchez, José Juan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137158/
https://www.ncbi.nlm.nih.gov/pubmed/37190034
http://dx.doi.org/10.3390/cells12081125
_version_ 1785032392417738752
author Pedrosa, Leire
Bedia, Carmen
Diao, Diouldé
Mosteiro, Alejandra
Ferrés, Abel
Stanzani, Elisabetta
Martínez-Soler, Fina
Tortosa, Avelina
Pineda, Estela
Aldecoa, Iban
Centellas, Marc
Muñoz-Tudurí, Marta
Sevilla, Ana
Sierra, Àngels
González Sánchez, José Juan
author_facet Pedrosa, Leire
Bedia, Carmen
Diao, Diouldé
Mosteiro, Alejandra
Ferrés, Abel
Stanzani, Elisabetta
Martínez-Soler, Fina
Tortosa, Avelina
Pineda, Estela
Aldecoa, Iban
Centellas, Marc
Muñoz-Tudurí, Marta
Sevilla, Ana
Sierra, Àngels
González Sánchez, José Juan
author_sort Pedrosa, Leire
collection PubMed
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 (PpIX) fluorescence measures demonstrated that the emission of PpIX 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.
format Online
Article
Text
id pubmed-10137158
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-101371582023-04-28 Preclinical Studies with Glioblastoma Brain Organoid Co-Cultures Show Efficient 5-ALA Photodynamic Therapy Pedrosa, Leire Bedia, Carmen Diao, Diouldé Mosteiro, Alejandra Ferrés, Abel Stanzani, Elisabetta Martínez-Soler, Fina Tortosa, Avelina Pineda, Estela Aldecoa, Iban Centellas, Marc Muñoz-Tudurí, Marta Sevilla, Ana Sierra, Àngels González Sánchez, José Juan Cells Article 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 (PpIX) fluorescence measures demonstrated that the emission of PpIX 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. MDPI 2023-04-10 /pmc/articles/PMC10137158/ /pubmed/37190034 http://dx.doi.org/10.3390/cells12081125 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Pedrosa, Leire
Bedia, Carmen
Diao, Diouldé
Mosteiro, Alejandra
Ferrés, Abel
Stanzani, Elisabetta
Martínez-Soler, Fina
Tortosa, Avelina
Pineda, Estela
Aldecoa, Iban
Centellas, Marc
Muñoz-Tudurí, Marta
Sevilla, Ana
Sierra, Àngels
González Sánchez, José Juan
Preclinical Studies with Glioblastoma Brain Organoid Co-Cultures Show Efficient 5-ALA Photodynamic Therapy
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 Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10137158/
https://www.ncbi.nlm.nih.gov/pubmed/37190034
http://dx.doi.org/10.3390/cells12081125
work_keys_str_mv AT pedrosaleire preclinicalstudieswithglioblastomabrainorganoidcoculturesshowefficient5alaphotodynamictherapy
AT bediacarmen preclinicalstudieswithglioblastomabrainorganoidcoculturesshowefficient5alaphotodynamictherapy
AT diaodioulde preclinicalstudieswithglioblastomabrainorganoidcoculturesshowefficient5alaphotodynamictherapy
AT mosteiroalejandra preclinicalstudieswithglioblastomabrainorganoidcoculturesshowefficient5alaphotodynamictherapy
AT ferresabel preclinicalstudieswithglioblastomabrainorganoidcoculturesshowefficient5alaphotodynamictherapy
AT stanzanielisabetta preclinicalstudieswithglioblastomabrainorganoidcoculturesshowefficient5alaphotodynamictherapy
AT martinezsolerfina preclinicalstudieswithglioblastomabrainorganoidcoculturesshowefficient5alaphotodynamictherapy
AT tortosaavelina preclinicalstudieswithglioblastomabrainorganoidcoculturesshowefficient5alaphotodynamictherapy
AT pinedaestela preclinicalstudieswithglioblastomabrainorganoidcoculturesshowefficient5alaphotodynamictherapy
AT aldecoaiban preclinicalstudieswithglioblastomabrainorganoidcoculturesshowefficient5alaphotodynamictherapy
AT centellasmarc preclinicalstudieswithglioblastomabrainorganoidcoculturesshowefficient5alaphotodynamictherapy
AT munoztudurimarta preclinicalstudieswithglioblastomabrainorganoidcoculturesshowefficient5alaphotodynamictherapy
AT sevillaana preclinicalstudieswithglioblastomabrainorganoidcoculturesshowefficient5alaphotodynamictherapy
AT sierraangels preclinicalstudieswithglioblastomabrainorganoidcoculturesshowefficient5alaphotodynamictherapy
AT gonzalezsanchezjosejuan preclinicalstudieswithglioblastomabrainorganoidcoculturesshowefficient5alaphotodynamictherapy