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Glioblastoma spheroids produce infiltrative gliomas in the rat brainstem

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Abstract

Purpose

Diffuse intrinsic pontine glioma (DIPG) is universally fatal without proven therapy other than radiation therapy for palliation. Representative animal models will play an essential role in the preclinical stage of future therapy development. To address the shortage of representative models, we created a novel infiltrative brainstem glioma model in rats based on glioblastoma spheroids.

Methods

Cells dissociated from glioblastoma spheroids grown from surgical specimens were implanted into the brainstem of NIH nude rats. Animals were serially assessed clinically and radiographically with magnetic resonance imaging (MRI). Tumors were further characterized using histology, immunohistochemistry, and cytogenetics.

Results

Tumor generation was successful in all animals receiving glioblastoma spheroid cells. The rats survived 17–25 weeks before severe symptoms developed. The tumors showed as diffuse hyperintense lesions on T2-weighted images. Histologically, they demonstrated cellular heterogeneity, and infiltrative and invasive features, with cells engorging vascular structures. The tumors were shown to comprise immature human origin glial tumor cells, with human epidermal growth factor receptor (EGFR) gene amplification and gain.

Conclusions

This study showed that cells from glioblastoma spheroids produced infiltrative gliomas in rat brainstem. The rat brainstem gliomas are radiographically and histologically accurate compared to DIPG. These tumors develop over several months that would allow sequential clinical and radiographic assessments of therapeutic interventions. This study demonstrated in principle the feasibility of developing patient-specific animal models based on putative cancer stem cells from biopsy or resection samples.

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Authors and Affiliations

  1. Department of Neurological Surgery, Weill Medical College of Cornell University, 525 East 68th Street, Box 99, New York, NY, 10065, USA

    Zhiping Zhou, Mark M. Souweidane & Jeffrey P. Greenfield

  2. NeuroSpine Institute, Bedford, NH, USA

    Neal Luther

  3. Weill Medical College of Cornell University, New York, NY, USA

    Ranjodh Singh

  4. Department of Neurological Surgery, Lenox Hill Hospital, Hofstra-NSLIJ School of Medicine, New York, NY, USA

    John A. Boockvar

  5. Department of Pediatrics, Weill Medical College of Cornell University, New York, NY, USA

    Mark M. Souweidane & Jeffrey P. Greenfield

  6. Department of Neurosurgery, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Mark M. Souweidane & Jeffrey P. Greenfield

Authors
  1. Zhiping Zhou
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  2. Neal Luther
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  3. Ranjodh Singh
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  4. John A. Boockvar
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Corresponding author

Correspondence to Zhiping Zhou.

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Conflicts of interest

The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

Financial and material support

Zhiping Zhou was partially supported by the Matthew Larson Foundation for Pediatric Brain Tumors.

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Zhou, Z., Luther, N., Singh, R. et al. Glioblastoma spheroids produce infiltrative gliomas in the rat brainstem. Childs Nerv Syst 33, 437–446 (2017). https://doi.org/10.1007/s00381-017-3344-y

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  • DOI: https://doi.org/10.1007/s00381-017-3344-y

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