One of the most aggressive forms of brain tumor is the high-grade glioma, or GBM. Patients diagnosed with these tumors have a median survival time of about 15 months, or just five to seven months for recurrent tumors. These grim statistics are thought to be the result of glioma stem cells, so researchers are looking to target these cells when developing new therapies. First, they need to develop realistic models of gliomas so they can study the biology of the stem cells and investigate their resistance to chemotheraphy.
Until now, researchers have mostly used 2D monolayers of glioma lines to study the tumors. These are limited, however, as these models do not allow the researchers to study the 3D environment of the tumor or study other factors such as cell-cell or cell-matrix interactions, spatial-temporal signaling or metabolic gradients. Therefore, most anti-glioma drugs that have been effective in vitro have performed poorly in clinical trials.
Now a group of researchers from Soochow University, Tsinghua University and the Tsinghua-Berkeley Shenzhen Institute, all in China, and Medprin Biotech GmbH in Germany, are working to create a glioma stem cell model using 3D bioprinting. Led by Tao Xu and Qin Lan, the researchers created a porous gelatine/alginate/fibrinogen hydrogel structure that mimics the extracellular matrix of glioma stem cells. They made the hydrogel more stable by adding the cross-linker transglutimase, a non-toxic transferase that exists naturally in the human body, to reinforce the gelatine.
“Our work shows that we can use bioprinting technology to build 3D glioma models. This is just beginning of our studies on the glioma microenvironment,” said team member Xingliang Dai.
The research has been published in an article entitled “3D bioprinted glioma stem cells for brain tumor model and applications of drug susceptibility,” which you can access here.
The researchers are now working to improve their current system as well as to optimize the inks used for bioprinting. They also need to improve the tumor model so that it more accurately mimics real glioma tumors.
“We have made much progress since the publication of the Biofabrication paper – including the fact that we observed differently expressed transcriptase profiles of the 3D bioprinted glioma stem cells compared to 2D-cultured ones,” said Xu.
“We are also happy to say that we have also received funding support from the National Natural Science Foundation, the National High Technology Research and Development Program of China (863 Program), and the Suzhou Science and Technology Project.”
Other research involving 3D bioprinted tumors has been promising, as these tumors give researchers a real idea of how an actual tumor will react to a certain drug or treatment. This dramatically speeds up the rate at which new drugs can get to market, as they’re much more likely to succeed in clinical trials if they’ve already been effective on a 3D printed tumor. These 3D printed tumors are the closest that researchers can get to studying and testing an actual tumor in the human body.
The researchers have also begun investigating the interactions between glioma stem cells and bone marrow mesenchymal stem cells, which can be done by fusing the two types of cells together during the bioprinting process.
“By applying the technology to glioma research, we have succeeded in shedding more light on glioma stem-cell behaviour, the glioma microenvironment, tumour-stromae interactions and glioma chemosensitivity,” said Xu.
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