Personalized Cancer Treatment Tested on Artificial Cancer
[Professor Dong-Woo Cho’s research team develops an in vitro cancer-vascular model using in situ 3D cell printing.]
In general, chemotherapy produces different results in each patient depending on the genomic and molecular background of the tumor. What if, by culturing cancer cells or stem cells collected from a patient, the drug response could be tested in advance and customized treatment found? A POSTECH research team has succeeded in producing an in vitro model of vascularized metastatic cancer using 3D bioprinting, enabling precision cancer treatment.
A research team led by Professor Dong-Woo Cho and Ph.D. candidate Won-Woo Cho of POSTECH’s Department of Mechanical Engineering in collaboration with Professor Byoung Soo Kim of Pusan National University and Professor Ge Gao from Beijing Institute of Technology have together developed an in situ 3D cell printing methodology that can directly print cancer spheroids that mimic the properties of metastatic melanoma within the decellularized extracellular matrix (dECM) bioink supporting bath. In addition, using this technology, the researchers succeeded in producing cancer spheroids with various diameters with blood vessels. The findings from this study were published as the inside front cover paper in Small Methods on July 14, 2021.
In order to engineer an in vitro model having properties similar to that of an actual tumor, it is essential to cultivate cancer cells in spheroids (3D cultured cells in an aggregated spherical shape). In particular, during tumor progression, the size and location of the tumor are important factors closely associated with metastatic potential of the cancer as they largely govern tumor hypoxia and angiogenesis of blood vessels. In order to accurately reproduce cancer metastasis, it is necessary to be able to simulate these characteristics. However, due to the lack of flexible technique, an in vitro model that mimics the pathological features of cancers has not been reported so far.
To this, the research team has developed a cell printing technology that can easily produce 3D cancer spheroids. This methodology allows to print 3D cancer spheroids (500–1000 µm) that can be scalable and positioned within the bioink. The research team confirmed the formation of the hypoxia region by controlling the size of the spheroid and compared metastatic gene expressions. In addition, an in vitro cancer-vascular model was produced by printing perfusable vascular endothelium system together with cancer spheroids in a bioink bath.
By printing the cancer spheroids at varied distances from the blood vessels, the researchers were able to observe the change in metastasis according to the distance between the blood vessels. In addition, the researchers verified that the vascular dysfunction and angiogenesis occurring in the tumor microenvironment and inflammation are generated via controlling the distance between the metastatic cancer unit (MCU) and the vascular endothelium system (VES).
“Through this research, we were able to print uniformly sized cancer spheroids at a desired location quickly,” explained Professor Dong-Woo Cho. “By printing cancer spheroids with in vitro blood vessels that mimic the structure of actual blood vessels, we were able to more accurately reproduce the cancer metastasis to blood vessels.”
Even for the same cancer, each patient has a different tumor progression and its genetic mutation also varies, making personalized treatment necessary. The possibility of producing personalized in vitro cancer-vascular model using cells derived from various patients has been verified through this study. The platform can elevate the reliability of personalized cancer treatments in the future.
This research was conducted with the support from the Creative Research Initiative Program and the Original Technology Research Program of the National Research Foundation of Korea.