Space-grown organoids better replicate aggressive glioblastoma tumors

Glioblastoma (GBM) is the most common malignant primary brain tumor in adults and is one of the most aggressive and deadly forms of cancer. It is difficult for surgeons to fully remove GBM because it often has microscopic "tentacles" that extend from the tumor into healthy brain tissue. GBM is also hard to treat because it creates an immunosuppressive microenvironment that helps the cancer evade immune attack and resist therapy.

To improve treatments, scientists must better understand the mechanisms involved in this complex disease, but accurately modeling GBM in the laboratory remains a challenge. Even sophisticated models called organoids, designed to mimic the structure and biology of human tumors, fail to fully reproduce key features of advanced GBM. When culturing cells on Earth, gravity causes them to settle, creating conditions that can interfere with the formation of complex 3D structures. That is why a team of researchers at the University of Notre Dame, led by Meenal Datta, took their research to space.

Leveraging the International Space Station (ISS) National Laboratory, the team grew three-dimensional organoids from GBM cells and innate immune cells that more closely replicate the structure and behavior of GBM tumors than organoids grown on Earth. In microgravity, cells can assemble into 3D structures with less interference from sedimentation, allowing researchers to better recreate the tumor architecture and cellular interactions seen in human disease. The results, recently published in PNAS, suggest that space-grown organoids could provide more realistic GBM models for studying cancer progression and testing new therapeutics.

In the investigation, which launched in 2024 with support from ISS National Lab Commercial Service Provider Space Tango, the Notre Dame team grew GBM-immune organoids in space for 40 days before returning them to Earth for analysis. The researchers found that in the space-grown organoids, genes related to inflammation, immune responses, tissue remodeling, and blood vessel formation were more active, and the levels of proteins associated with more aggressive GBM biology were higher. Additionally, the space-grown organoids showed a more immunosuppressive tumor microenvironment, a hallmark of advanced GBM that helps tumors resist the body's immune defenses.

Datta said the study also produced the first comprehensive multiomics dataset from space-grown organoids, providing insights into gene activity, protein expression, and how cells interact and are organized within the tissue.

"By growing GBM organoids on the ISS, we demonstrated that microgravity fuels a model phenotype that recapitulates human tumors better and faster than we achieve on the ground. This work helps lay the foundation for a new era of orbital oncology that moves cancer research from bedside to orbit and back again," said Datta, the Jane Schoelch DeFlorio Collegiate Professor of Aerospace and Mechanical Engineering at the University of Notre Dame.

To build on these promising results, Datta and her team have launched two additional ISS investigations using patient-derived GBM-immune organoids, with the most recent flying on the SpaceX CRS-35 mission for NASA. By providing models that more fully capture the complex architecture and biology of advanced tumors, space-grown organoids could help researchers better understand GBM progression and accelerate the development of new therapies for patients on Earth.

This investigation is one of many cancer-focused projects supported by the ISS National Lab. Through a growing portfolio that spans cancer biology, therapeutic development, and advanced disease modeling, researchers are leveraging the unique environment of space to address some of the most difficult challenges in oncology.

"Dr. Datta and her team at the Tumor Immune Microenvironment and Mechanics Laboratory brought their expertise in one of the most aggressive and incurable brain cancers to space, where they demonstrated microgravity's unique ability to improve organoid models that function as 'mini tumors.' By combining human-derived glioblastoma cells with immune cells in space, this work could prove to be a landmark study in the effort to better understand and treat GBM and other aggressive cancers," said ISS National Lab Chief Scientist Michael Roberts.

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International Space Station U.S. National Laboratory

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