3D extracellular matrix microenvironment in bioengineered tissue models of primary pediatric and adult brain tumors

Disha Sood, Min Tang-Schomer, Dimitra Pouli, Craig Mizzoni, Nicole Raia, Albert Tai, Knarik Arkun, Julian Wu, Lauren D. Black, Bjorn Scheffler, Irene Georgakoudi, Dennis A. Steindler and David L. Kaplan ()
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Disha Sood: Tufts University
Min Tang-Schomer: Jackson Laboratory for Genomic Medicine
Dimitra Pouli: Tufts University
Craig Mizzoni: Tufts University
Nicole Raia: Tufts University
Albert Tai: Tufts University School of Medicine
Knarik Arkun: Tufts Medical Center
Julian Wu: Tufts Medical Center
Lauren D. Black: Tufts University
Bjorn Scheffler: University of Florida, McKnight Brain Institute
Irene Georgakoudi: Tufts University
Dennis A. Steindler: University of Florida, McKnight Brain Institute
David L. Kaplan: Tufts University

Nature Communications, 2019, vol. 10, issue 1, 1-14

Abstract: Abstract Dynamic alterations in the unique brain extracellular matrix (ECM) are involved in malignant brain tumors. Yet studies of brain ECM roles in tumor cell behavior have been difficult due to lack of access to the human brain. We present a tunable 3D bioengineered brain tissue platform by integrating microenvironmental cues of native brain-derived ECMs and live imaging to systematically evaluate patient-derived brain tumor responses. Using pediatric ependymoma and adult glioblastoma as examples, the 3D brain ECM-containing microenvironment with a balance of cell-cell and cell-matrix interactions supports distinctive phenotypes associated with tumor type-specific and ECM-dependent patterns in the tumor cells’ transcriptomic and release profiles. Label-free metabolic imaging of the composite model structure identifies metabolically distinct sub-populations within a tumor type and captures extracellular lipid-containing droplets with potential implications in drug response. The versatile bioengineered 3D tumor tissue system sets the stage for mechanistic studies deciphering microenvironmental role in brain tumor progression.

Date: 2019
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DOI: 10.1038/s41467-019-12420-1

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