Joint Team Led by Professors Wang Jian and Rolf Bjerkvig Achieves New Breakthrough in Brain Organoid Models for Glioma Research
inputtime：2025-12-18 15:00:00 From：Qilu Hospital
Recently, a joint research team led by Professor Wang Jian of the Institute of Brain and Brain-Inspired Research at Shandong University, in collaboration with Professor Rolf Bjerkvig of the University of Bergen, Norway, who also serves as an Adjunct Chair Professor at Shandong University, reported a major advance in brain organoid modeling for glioma research. Their study, entitled “Development of a Highly Differentiated Rat Brain Organoid Model for Exploring Glioblastoma Invasion Dynamics and Therapy,” was published in Neuro-Oncology, a leading journal in neuro-oncology (CAS Tier 1, TOP journal; Impact Factor: 16.4).
Dr. Zhou Wenjing, attending physician at Shandong Provincial Hospital affiliated with Shandong First Medical University; Dr. Elena Martinez-Garcia of the Luxembourg Institute of Health; and Dr. Katharina Sarnow, a postdoctoral researcher at Harvard University, are co–first authors of the study. Professors Wang Jian and Rolf Bjerkvig served as co–corresponding authors.
Addressing a critical limitation of existing brain organoid models—particularly those derived from human induced pluripotent stem cells (iPSCs), which often fail to achieve terminal differentiation and cannot fully recapitulate the mature brain microenvironment—the team innovatively developed a highly differentiated brain organoid model derived from rat embryonic brain tissue. After 21 days of in vitro culture, the model formed a complex and well-organized structure containing myelinated neurons, oligodendrocytes, astrocytes, microglia, and functional synapses. In terms of cellular composition, molecular expression profiles, and neurotransmitter synthesis capacity, the organoids closely resembled the mature rat brain.
Using this model, the researchers co-cultured the organoids with five human glioma stem cell lines exhibiting distinct invasive properties, enabling real-time, dynamic, and quantitative analysis of glioma invasion behavior. The system faithfully reproduced the growth and invasion patterns observed in vivo. Notably, through single-cell sequencing and related approaches, the team demonstrated for the first time that a mature brain organoid microenvironment can actively “reprogram” tumor cells, inducing a metabolic shift toward glycolysis and enhancing invasive capacity. This process was shown to be partially mediated by extracellular vesicles released by the organoids.
In addition, the platform was successfully used to evaluate the inhibitory effects of therapeutics with different mechanisms of action, including TGF-β inhibitors and AMPA receptor antagonists such as perampanel, on glioma invasion. These results validate the model’s potential as a high-throughput platform for anti-invasion drug screening.
With strong physiological relevance to the human brain, as well as advantages in scalability, reproducibility, and cost efficiency, this brain organoid model overcomes key limitations of existing systems. It provides a powerful tool for in-depth investigation of glioma invasion mechanisms and opens new avenues for rapid evaluation of novel anti-invasive therapies, advancing precision research in neuro-oncology.
Article link:
https://pubmed.ncbi.nlm.nih.gov/41284925/
Dr. Zhou Wenjing, attending physician at Shandong Provincial Hospital affiliated with Shandong First Medical University; Dr. Elena Martinez-Garcia of the Luxembourg Institute of Health; and Dr. Katharina Sarnow, a postdoctoral researcher at Harvard University, are co–first authors of the study. Professors Wang Jian and Rolf Bjerkvig served as co–corresponding authors.
Addressing a critical limitation of existing brain organoid models—particularly those derived from human induced pluripotent stem cells (iPSCs), which often fail to achieve terminal differentiation and cannot fully recapitulate the mature brain microenvironment—the team innovatively developed a highly differentiated brain organoid model derived from rat embryonic brain tissue. After 21 days of in vitro culture, the model formed a complex and well-organized structure containing myelinated neurons, oligodendrocytes, astrocytes, microglia, and functional synapses. In terms of cellular composition, molecular expression profiles, and neurotransmitter synthesis capacity, the organoids closely resembled the mature rat brain.
Using this model, the researchers co-cultured the organoids with five human glioma stem cell lines exhibiting distinct invasive properties, enabling real-time, dynamic, and quantitative analysis of glioma invasion behavior. The system faithfully reproduced the growth and invasion patterns observed in vivo. Notably, through single-cell sequencing and related approaches, the team demonstrated for the first time that a mature brain organoid microenvironment can actively “reprogram” tumor cells, inducing a metabolic shift toward glycolysis and enhancing invasive capacity. This process was shown to be partially mediated by extracellular vesicles released by the organoids.
In addition, the platform was successfully used to evaluate the inhibitory effects of therapeutics with different mechanisms of action, including TGF-β inhibitors and AMPA receptor antagonists such as perampanel, on glioma invasion. These results validate the model’s potential as a high-throughput platform for anti-invasion drug screening.
With strong physiological relevance to the human brain, as well as advantages in scalability, reproducibility, and cost efficiency, this brain organoid model overcomes key limitations of existing systems. It provides a powerful tool for in-depth investigation of glioma invasion mechanisms and opens new avenues for rapid evaluation of novel anti-invasive therapies, advancing precision research in neuro-oncology.
Article link:
https://pubmed.ncbi.nlm.nih.gov/41284925/
