Patient‐ and xenograft‐derived organoids recapitulate pediatric brain tumor features and patient treatments
Abstract Brain tumors are the leading cause of cancer‐related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancers are limited and hard to establish. We present a protocol that enables efficient generation, expansion...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Springer Nature
2023-11-01
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| Series: | EMBO Molecular Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.15252/emmm.202318199 |
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| author | Chiara Lago Aniello Federico Gloria Leva Norman L Mack Benjamin Schwalm Claudio Ballabio Matteo Gianesello Luana Abballe Isabella Giovannoni Sofia Reddel Sabrina Rossi Nicolas Leone Andrea Carai Angela Mastronuzzi Alessandra Bisio Alessia Soldano Concetta Quintarelli Franco Locatelli Marcel Kool Evelina Miele Luca Tiberi |
| author_facet | Chiara Lago Aniello Federico Gloria Leva Norman L Mack Benjamin Schwalm Claudio Ballabio Matteo Gianesello Luana Abballe Isabella Giovannoni Sofia Reddel Sabrina Rossi Nicolas Leone Andrea Carai Angela Mastronuzzi Alessandra Bisio Alessia Soldano Concetta Quintarelli Franco Locatelli Marcel Kool Evelina Miele Luca Tiberi |
| author_sort | Chiara Lago |
| collection | DOAJ |
| description | Abstract Brain tumors are the leading cause of cancer‐related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancers are limited and hard to establish. We present a protocol that enables efficient generation, expansion, and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient‐derived organoids (PDOs) from ependymomas, medulloblastomas, low‐grade glial tumors, and patient‐derived xenograft organoids (PDXOs) from medulloblastoma xenografts. PDOs and PDXOs recapitulate histological features, DNA methylation profiles, and intratumor heterogeneity of the tumors from which they were derived. We also showed that PDOs can be xenografted. Most interestingly, when subjected to the same routinely applied therapeutic regimens, PDOs respond similarly to the patients. Taken together, our study highlights the potential of PDOs and PDXOs for research and translational applications for personalized medicine. |
| first_indexed | 2024-03-07T16:47:56Z |
| format | Article |
| id | doaj.art-27709dc824264046a65fac5ef01127a4 |
| institution | Directory Open Access Journal |
| issn | 1757-4676 1757-4684 |
| language | English |
| last_indexed | 2025-02-18T14:20:26Z |
| publishDate | 2023-11-01 |
| publisher | Springer Nature |
| record_format | Article |
| series | EMBO Molecular Medicine |
| spelling | doaj.art-27709dc824264046a65fac5ef01127a42024-10-28T08:48:29ZengSpringer NatureEMBO Molecular Medicine1757-46761757-46842023-11-01151212810.15252/emmm.202318199Patient‐ and xenograft‐derived organoids recapitulate pediatric brain tumor features and patient treatmentsChiara Lago0Aniello Federico1Gloria Leva2Norman L Mack3Benjamin Schwalm4Claudio Ballabio5Matteo Gianesello6Luana Abballe7Isabella Giovannoni8Sofia Reddel9Sabrina Rossi10Nicolas Leone11Andrea Carai12Angela Mastronuzzi13Alessandra Bisio14Alessia Soldano15Concetta Quintarelli16Franco Locatelli17Marcel Kool18Evelina Miele19Luca Tiberi20Armenise‐Harvard Laboratory of Brain Disorders and Cancer, CIBIOHopp Children's Cancer Center (KiTZ)Armenise‐Harvard Laboratory of Brain Disorders and Cancer, CIBIOHopp Children's Cancer Center (KiTZ)Hopp Children's Cancer Center (KiTZ)Armenise‐Harvard Laboratory of Brain Disorders and Cancer, CIBIOArmenise‐Harvard Laboratory of Brain Disorders and Cancer, CIBIODepartment of Onco‐Hematology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS)Pathology Unit, Bambino Gesù Children's Hospital, IRCCSDepartment of Onco‐Hematology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS)Pathology Unit, Bambino Gesù Children's Hospital, IRCCSPathology Unit, Bambino Gesù Children's Hospital, IRCCSNeurosurgery Unit, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCSDepartment of Onco‐Hematology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS)Laboratory of Radiobiology, CIBIODepartment of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA)Department of Onco‐Hematology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS)Department of Onco‐Hematology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS)Hopp Children's Cancer Center (KiTZ)Department of Onco‐Hematology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS)Armenise‐Harvard Laboratory of Brain Disorders and Cancer, CIBIOAbstract Brain tumors are the leading cause of cancer‐related death in children. Experimental in vitro models that faithfully capture the hallmarks and tumor heterogeneity of pediatric brain cancers are limited and hard to establish. We present a protocol that enables efficient generation, expansion, and biobanking of pediatric brain cancer organoids. Utilizing our protocol, we have established patient‐derived organoids (PDOs) from ependymomas, medulloblastomas, low‐grade glial tumors, and patient‐derived xenograft organoids (PDXOs) from medulloblastoma xenografts. PDOs and PDXOs recapitulate histological features, DNA methylation profiles, and intratumor heterogeneity of the tumors from which they were derived. We also showed that PDOs can be xenografted. Most interestingly, when subjected to the same routinely applied therapeutic regimens, PDOs respond similarly to the patients. Taken together, our study highlights the potential of PDOs and PDXOs for research and translational applications for personalized medicine.https://doi.org/10.15252/emmm.202318199brain tumorsorganoidspatient‐derivedpediatric cancertranslational applications |
| spellingShingle | Chiara Lago Aniello Federico Gloria Leva Norman L Mack Benjamin Schwalm Claudio Ballabio Matteo Gianesello Luana Abballe Isabella Giovannoni Sofia Reddel Sabrina Rossi Nicolas Leone Andrea Carai Angela Mastronuzzi Alessandra Bisio Alessia Soldano Concetta Quintarelli Franco Locatelli Marcel Kool Evelina Miele Luca Tiberi Patient‐ and xenograft‐derived organoids recapitulate pediatric brain tumor features and patient treatments EMBO Molecular Medicine brain tumors organoids patient‐derived pediatric cancer translational applications |
| title | Patient‐ and xenograft‐derived organoids recapitulate pediatric brain tumor features and patient treatments |
| title_full | Patient‐ and xenograft‐derived organoids recapitulate pediatric brain tumor features and patient treatments |
| title_fullStr | Patient‐ and xenograft‐derived organoids recapitulate pediatric brain tumor features and patient treatments |
| title_full_unstemmed | Patient‐ and xenograft‐derived organoids recapitulate pediatric brain tumor features and patient treatments |
| title_short | Patient‐ and xenograft‐derived organoids recapitulate pediatric brain tumor features and patient treatments |
| title_sort | patient and xenograft derived organoids recapitulate pediatric brain tumor features and patient treatments |
| topic | brain tumors organoids patient‐derived pediatric cancer translational applications |
| url | https://doi.org/10.15252/emmm.202318199 |
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