International experience in the development of patient-derived xenograft models of diffuse intrinsic pontine glioma

Maria Tsoli, Han Shen, Chelsea Mayoh, Laura Franshaw, Anahid Ehteda, Danielle Upton, Diana Carvalho, Maria Vinci, Michael H. Meel, Dannis van Vuurden, Alexander Plessier, David Castel, Rachid Drissi, Michael Farrell, Jane Cryan, Darach Crimmins, John Caird, Jane Pears, Stephanie Francis, Louise E. A. LudlowAndrea Carai, Angela Mastronuzzi, Bing Liu, Jordan Hansford, Nick Gottardo, Tim Hassall, Maria Kirby, Maryam Fouladi, Cynthia Hawkins, Michelle Monje, Jacques Grill, Chris Jones, Esther Hulleman, David S. Ziegler

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Purpose: Diffuse intrinsic pontine glioma is the most aggressive form of high grade glioma in children with no effective therapies. There have been no improvements in survival in part due poor understanding of underlying biology, and lack of representative in vitro and in vivo models. Recently, it has been found feasible to use both biopsy and autopsy tumors to generate cultures and xenograft models. Methods: To further model development, we evaluated the collective international experience from 8 collaborating centers to develop DIPG pre-clinical models from patient-derived autopsies and biopsies. Univariate and multivariate analysis was performed to determine key factors associated with the success of in vitro and in vivo PDX development. Results: In vitro cultures were successfully established from 57% of samples (84.2% of biopsies and 38.2% of autopsies). Samples transferred in DMEM media were more likely to establish successful culture than those transported in Hibernate A. In vitro cultures were more successful from biopsies (84.2%) compared with autopsies (38.2%) and as monolayer on laminin-coated plates than as neurospheres. Primary cultures successfully established from autopsy samples were more likely to engraft in animal models than cultures established from biopsies (86.7% vs. 47.4%). Collectively, tumor engraftment was more successful when DIPG samples were directly implanted in mice (68%), rather than after culturing (40.7%). Conclusion: This multi-center study provides valuable information on the success rate of establishing patient-derived pre-clinical models of DIPG. The results can lead to further optimization of DIPG model development and ultimately assist in the investigation of new therapies for this aggressive pediatric brain tumor.
Original languageEnglish
Pages (from-to)253-263
Number of pages11
JournalJournal of Neuro-Oncology
Volume141
Issue number2
Early online date2018
DOIs
Publication statusPublished - 30 Jan 2019

Cite this