Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists create brain-mimicking environment to grow 3D tissue models of brain tumors

04.10.2019

Use of brain-like extracellular matrix allows cell growth and treatment to more closely replicate physiological response

A team of Tufts University-led researchers has developed three-dimensional (3D) human tissue culture models of pediatric and adult brain cancers in a brain-mimicking microenvironment, a significant advancement for the study of brain tumor biology and pharmacological response. The study was published today in Nature Communications.


Inset shows a donut-shaped 3D silk scaffold (represented as schematic in background) that has been treated with fetal pig brain extracellular matrix and seeded with glioblastoma cells. Spherical growths of the tumor cells (~1mm dark spots - indicated by arrow) are observed after 1.5 months.

Credit: Disha Sood & David Kaplan, Tufts University

The researchers created models that include brain-derived extracellular matrix (ECM) - the complex network of proteins and amino acids with bound sugars naturally found in the brain.

The ECM not only provides support for surrounding neural tissue, but also helps to guide cell growth and development. Alterations in ECM composition have been associated with brain tumor progression, which in turn alters patterns of genetic and protein expression in the tumor cells.

Earlier studies have noted this important two-way interaction between tumor cells and the surrounding ECM, and observed that the protein composition in the ECM can either prevent or allow the further diffusion of tumor cells in the brain.

In order to better understand the dynamic interactions between tumors and the ECM, the study authors developed a 3D in vitro system in which they can examine different ECM components and define their contribution to tumor development, as well as tumor response to drug treatments.

The study focused on two common types of brain tumors, both with particularly dismal prognoses - ependymoma, which occurs in young children, and glioblastoma in adults, which results in a median survival of 1-2 years post diagnosis.

In an important advance, the ECM-containing 3D matrix in this study has allowed for the propagation and study of primary tumor cells taken directly from the patient, and to grow them in an environment more similar to the brain.

Previous studies examined established tumor cell lines -- not necessarily the tumor of interest -- on 3D scaffolds or spheroids without the ECM, or spread cells out in two dimensions (plating), eliciting cell behavior not seen in their natural environment

"The power of this platform is that we can tune the composition of the ECM to find out the role of each component in tumor growth, and we can see the effect on tumor cells derived directly from the patient," said David Kaplan, Stern Family Professor of Engineering, chair of the Department of Biomedical Engineering at Tufts' School of Engineering and program faculty member at the Sackler School of Graduate Biomedical Sciences.

"Another important feature is that we can track the 3D growth of cells with non-invasive two-photon excited fluorescence metabolic imaging via the contributions of Irene Georgakoudi's team on the project. In other words, we can use non-invasive imaging to assess if they are viable and growing, or stressed and dying, in real-time."

Among the findings revealed in the study was that fetal ECM, which contains higher levels of collagen, HA and certain CSPGs, was better at supporting tumor growth than adult ECM in the 3D cultures (both fetal and adult ECMs were derived from pig brains). That result correlates with the notion that brain cancers tend to alter the ECM so its composition becomes more "fetal-like" to support their growth, according to the researchers.

Another key finding was the appearance of lipid (fat) droplets being released by the adult glioblastoma cells which may contribute to lowering the drug sensitivity of many glioblastoma cells (possibly by absorbing the drugs).

This may be correlated with poor survival both in the 3D tissue model and in patients. The droplets have not been observed in vitro prior to these experiments, suggesting that this model is a robust system to study the behavior of brain tumors in the lab.

The application of engineering solutions (in this case, the development of a 3D silk-based matrix) to improve the study of the brain is a collaborative effort taken on by the authors as part of the Initiative for Neural Science, Disease & Engineering (INSciDE@Tufts).

"With this platform, we have the potential to better understand what dictates the invasive behavior of brain tumors and screen drugs for their effect on tumor growth of patient-derived cells," said Disha Sood, graduate student in Kaplan's lab and first author of the study.

"Although it's a preliminary notion, the ability to maintain viable cultures of patient-derived tumor cells and metabolically track them non-invasively, suggests the possibility of monitoring the cells' behavior and drug sensitivity over time, to inform treatment decisions."

###

Other authors contributing to the study are Dmitra Pouli, Craig Mizzoni, and Nicole Raia, graduate students in the Department of Biomedical Engineering in the School of Engineering at Tufts University; Lauren D. Black III, associate professor, and Irene Georgakoudi, professor of biomedical engineering at Tufts School of Engineering; Albert Tai and Knarik Arkun, assistant professors, and Julian Wu, associate chair of neurosurgery at Tufts Medical Center as well as a professor at Tufts University School of Medicine; Dennis Steindler, senior scientist at the Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University; Bjorn Scheffler, professor at the German Cancer Consortium (DKTK); and Min Tang-Schomer of the Jackson Laboratory in Connecticut.

This work was funded by the U.S. National Institutes of Health (NIH) P41 Tissue Engineering Resource Center grant #EB002520, NIH R01 grant #NS092847, and the NIH Research Infrastructure grant #S10 OD021624 766, and National Science Foundation Major Research Instrumentation grant #1531683, and the U.S. Department of Agriculture's Agricultural Research Service. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Sood, D., Tang-Schomer, M., Pouli, D., Mizzoni, C., Raia, N., Tai, A., Knarik, A., Wu, J., Black III, L.D., Scheffler, B., Georgakoudi, I., Steindler, D.A. and Kaplan, D.L. "3D extracellular matrix microenvironment in bioengineered tissue models of primary pediatric and adult brain tumors." Nature Communications. (October 4, 2019); DOI: 10.1038/s41467-019-12420-1.

About Tufts University

Tufts University, located on campuses in Boston, Medford/Somerville and Grafton, Massachusetts, and in Talloires, France, is recognized among the premier research universities in the United States. Tufts enjoys a global reputation for academic excellence and for the preparation of students as leaders in a wide range of professions. A growing number of innovative teaching and research initiatives span all Tufts campuses, and collaboration among the faculty and students in the undergraduate, graduate and professional programs across the university's schools is widely encouraged.

Media Contact

Mike Silver
mike.silver@tufts.edu
617-627-0545

 @TuftsPR

http://www.tufts.edu 

Mike Silver | EurekAlert!
Further information:
http://dx.doi.org/10.1038/s41467-019-12420-1

More articles from Life Sciences:

nachricht New deep-water coral discovered
22.10.2019 | Smithsonian Tropical Research Institute

nachricht DNA-reeling bacteria yield new insight on how superbugs acquire drug-resistance
22.10.2019 | Indiana University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: A cavity leads to a strong interaction between light and matter

Researchers have succeeded in creating an efficient quantum-mechanical light-matter interface using a microscopic cavity. Within this cavity, a single photon is emitted and absorbed up to 10 times by an artificial atom. This opens up new prospects for quantum technology, report physicists at the University of Basel and Ruhr-University Bochum in the journal Nature.

Quantum physics describes photons as light particles. Achieving an interaction between a single photon and a single atom is a huge challenge due to the tiny...

Im Focus: Solving the mystery of quantum light in thin layers

A very special kind of light is emitted by tungsten diselenide layers. The reason for this has been unclear. Now an explanation has been found at TU Wien (Vienna)

It is an exotic phenomenon that nobody was able to explain for years: when energy is supplied to a thin layer of the material tungsten diselenide, it begins to...

Im Focus: An ultrafast glimpse of the photochemistry of the atmosphere

Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich have explored the initial consequences of the interaction of light with molecules on the surface of nanoscopic aerosols.

The nanocosmos is constantly in motion. All natural processes are ultimately determined by the interplay between radiation and matter. Light strikes particles...

Im Focus: Shaping nanoparticles for improved quantum information technology

Particles that are mere nanometers in size are at the forefront of scientific research today. They come in many different shapes: rods, spheres, cubes, vesicles, S-shaped worms and even donut-like rings. What makes them worthy of scientific study is that, being so tiny, they exhibit quantum mechanical properties not possible with larger objects.

Researchers at the Center for Nanoscale Materials (CNM), a U.S. Department of Energy (DOE) Office of Science User Facility located at DOE's Argonne National...

Im Focus: Novel Material for Shipbuilding

A new research project at the TH Mittelhessen focusses on the development of a novel light weight design concept for leisure boats and yachts. Professor Stephan Marzi from the THM Institute of Mechanics and Materials collaborates with Krake Catamarane, which is a shipyard located in Apolda, Thuringia.

The project is set up in an international cooperation with Professor Anders Biel from Karlstad University in Sweden and the Swedish company Lamera from...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

International Symposium on Functional Materials for Electrolysis, Fuel Cells and Metal-Air Batteries

02.10.2019 | Event News

NEXUS 2020: Relationships Between Architecture and Mathematics

02.10.2019 | Event News

Optical Technologies: International Symposium „Future Optics“ in Hannover

19.09.2019 | Event News

 
Latest News

New deep-water coral discovered

22.10.2019 | Life Sciences

DNA-reeling bacteria yield new insight on how superbugs acquire drug-resistance

22.10.2019 | Life Sciences

Heat Pumps with Climate-Friendly Refrigerant Developed for Indoor Installation

22.10.2019 | Power and Electrical Engineering

VideoLinks
Science & Research
Overview of more VideoLinks >>>