2. Academic Validation
  3. Patient- and xenograft-derived organoids recapitulate pediatric brain tumor features and patient treatments

Patient- and xenograft-derived organoids recapitulate pediatric brain tumor features and patient treatments

  • EMBO Mol Med. 2023 Nov 30:e18199. doi: 10.15252/emmm.202318199.
Chiara Lago 1,  Aniello Federico 2 3,  Gloria Leva 1,  Norman L Mack 2 3,  Benjamin Schwalm 2 3,  Claudio Ballabio 1,  Matteo Gianesello 1,  Luana Abballe 4,  Isabella Giovannoni 5,  Sofia Reddel 4,  Sabrina Rossi 5,  Nicolas Leone 5,  Andrea Carai 6,  Angela Mastronuzzi 4,  Alessandra Bisio 7 8,  Alessia Soldano 9,  Concetta Quintarelli 4,  Franco Locatelli 4 10,  Marcel Kool 2 3 11 12,  Evelina Miele 4,  Luca Tiberi 1
Affiliations

Affiliations

  • 1 Armenise-Harvard Laboratory of Brain Disorders and Cancer, CIBIO, Trento, Italy.
  • 2 Hopp Children's Cancer Center (KiTZ), Heidelberg, Germany.
  • 3 Division of Paediatric Neurooncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Heidelberg, Germany.
  • 4 Department of Onco-Hematology, Cell and Gene Therapy, Bambino Gesù Children's Hospital, Scientific Institute for Research, Hospitalization and Healthcare (IRCCS), Rome, Italy.
  • 5 Pathology Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • 6 Neurosurgery Unit, Department of Neurosciences, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
  • 7 Laboratory of Radiobiology, CIBIO, Trento, Italy.
  • 8 Trento Institute for Fundamental Physics and Application, TIFPA, Trento, Italy.
  • 9 Department of Neuroscience, Scuola Internazionale Superiore di Studi Avanzati (SISSA), Trieste, Italy.
  • 10 Catholic University of the Sacred Heart, Rome, Italy.
  • 11 Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands.
  • 12 University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
PMID: 38037472 DOI: 10.15252/emmm.202318199
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.

Keywords

brain tumors; organoids; patient-derived; pediatric cancer; translational applications.

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