image: The illustration highlights the strengths of mechanical dissociation in preserving the native tumor microenvironment and ensuring viability, alongside the advantages of enzymatic digestion for standardization, high-throughput applications, and gene editing. Combined approaches are tailored for specific tissue types, optimizing the generation of patient-derived organoids for advanced cancer research.
Credit: Shichao Duan, Henan University People’s Hospital
Cancer remains one of the most complex diseases, with its diverse molecular profiles and cellular compositions posing significant challenges for treatment. Traditional methods of cancer research, such as two-dimensional cell cultures and animal models, often fail to capture the full complexity of human cancers, particularly the three-dimensional structures and microenvironmental interactions of solid tumors. This gap has fueled the need for more advanced models that can accurately mirror the genetic and phenotypic diversity of tumors, driving the development of sophisticated tumor modeling techniques.
A team of researchers from Henan Provincial People’s Hospital and the Academy of Medical Science have made substantial contributions to the understanding of cancer biology. Published (DOI: 10.26599/CO.2024.9410009) in Cell Organoid on December 25, 2024. While comparing mechanical dissociation and enzymatic digestion for generating patient-derived organoids (PDOs), they emphasize the importance of maintaining the tumor microenvironment, which mechanical dissociation preserves more effectively. This method retains the tumor’s architecture and cellular heterogeneity, essential for accurately modeling human cancers. In contrast, enzymatic digestion disrupts the native tissue environment but yields a more homogeneous cell population, ideal for large-scale drug screening due to its reproducibility and controllability. Additionally, the authors highlight the influence of these techniques on organoid properties such as stemness, differentiation potential, and tumor heterogeneity—factors that are crucial for the development of personalized medicine, and explore the implications for long-term organoid culture, which is vital for understanding tumor evolution, drug resistance, and metastasis. These findings are set to shape the future of organoid-based cancer models and deepen our understanding of tumor biology.
Dr. Haijun Li, the corresponding author of the study, comments, “Our article offers new insights into the intricacies of mechanical and enzymatic dissociation methods, providing researchers with a valuable guide to selecting the best tissue dissociation strategy for their specific research goals. This will help advance the field of organoid-based cancer models.”
The review on tissue dissociation techniques is poised to make a significant impact on oncology research, especially for solid tumor. By refining organoid derivation methods, scientists can create more accurate cancer models, enhancing drug screening processes and paving the way for more personalized and effective treatment strategies. This advancement could revolutionize cancer therapy, potentially leading to better patient outcomes through treatments tailored to individual tumor characteristics and therapeutic responses.
This work was supported by National Natural Science Foundation of China (No. U1904166); Henan Medical Science and technology research plan (No. SBGJ2018072); Henan province natural science foundation (No. 242300421284).
About Cell Organoid
Cell Organoid aims to provide a worldwide platform for research into all aspects of organoids and their applications in medicine. It is an open access, peer-reviewed journal that publishes high-quality articles dealing with a wide range of basic research, clinical and translational medicine study topics in the field.
Journal website: https://www.sciopen.com/journal/3007-6552
Submission site: https://mc03.manuscriptcentral.com/cellorganoid
Journal
Cell Organoid
Article Title
The pros and cons of mechanical dissociation and enzymatic digestion in patient-derived organoid cultures for solid tumor
Article Publication Date
12-Dec-2024