The Gastric Organoids
- Challenges in research on human stomach and gastric cancer
- Opportunities on organoid technology in scientific research
- Application of gastric organoids in research
- Example on limitation of current organoid research
- Some future trends on organoid-related cancer research
- Selected compositions for gastric epithelial organoid culture recipe by Lab-A-Porter
Challenges in research on human stomach and gastric cancer
- These models establish unnatural geometric and mechanical constraints by adhering cells to an artificial substrate (either plastic or glass). 
- Such as culture affects cell polarity and therefore, potentially, tumour phenotypes. 
Transgenic animal models of gastric cancer tumorigenesis have been advanced. 
- However, these models have all shown limitations connected to genetic background irrelevance, animal resistance and the inability to allow examination of the mechanisms that characterize the aggressive metastasis tumours 
Opportunities on organoid technology in scientific research
Particularly, patient-derived organoids biobanks of gastric cancer act as a useful tool in studying gastric cancer biology:
- Gastric cancer ranking as the fifth most common malignancy, the third leading cause of cancer-related deaths. 
- Gastric cancer is a heterogenous disease displaying many different histological and molecular subtypes [1,3]
- The prognosis of gastric cancer is poor and most advanced forms of the disease remain incurable. 
- Although treatment effectiveness has improved during the past decade, gastric cancer survival rates remain poor. 
- This suggests an urgent need to advance innovative therapies available to gastric cancer patients. 
Patient-derived organoids biobanks provide a great advantage over classical 2D cell lines in gastric tumour research 
- Nanki and colleagues have generated 37 PDO lines. 
- They obtained patient-derived organoids of all gastric tumour subtypes except for the Epstein-Barr virus-associated one. 
- Established patient-derived organoids recapitulated the same histopathological features as the original tumour. 
- Yan and colleagues have established 46 PDOs. 
- They classified them into 4 gastric subtypes with comparable mutational spectra. 
- They observed sub-clonal tumour evolution by comparing multiple biopsies obtained from the primary tumour or even metastasis of the same patient. 
- Nanki and colleagues have generated 37 PDO lines. 
Application of gastric organoids in research
- Use organoids as a preclinical model
Organoids are 3D cultures that can retain the morphologies and gene expression profiles of their organs of origin .
- Use human and mouse organoids for disease modelling
For example, the use of gastric organoids has facilitated many important discoveries regarding H. pylori pathogenesis , pediatric gastric homeostasis and pediatric mucosal diseases 
- Use patient-derived organoids to personalize medicine for gastric cancer patients
Patient-derived organoids can be derived from endoscopic tumour biopsies, which maintain heterogeneity in culture. 
- They can be rapidly established and expanded in a relatively short time for in vitro drug screening experiments, for therapy prediction and guidance. 
Example on limitation of current organoid research
- Organoids only contain epithelial layers without tissue microenvironments, such as the immune system and nervous system. 
- Fully maturation to adult organs or tissues is a bottleneck needed to be addressed. 
- Dependence on the extracellular matrix or basement membrane extract of current organoids. 
- The culture medium needs to be further refined for the long-term expansion of some organoids. 
- Growth factors or molecular inhibitors in culture medium might have some effects on drug responses of organoids. 
Some future trends on organoid-related cancer research
- Current data suggest a good predictive value of patient-derived organoids in drug and radiation assays, even if the overall mutational landscape is unknown.
- The evolution of translational research, through its applications with patient-derived tumour organoid models, makes it emerge as a crucial strategy in personalized medicine programs. 
- New clinical trials are required to further validate the benefits of gastric cancer patient-derived tumour organoids in personalized medicine.
- To assess the correlation between the in vivo primary tumour response and the ex vivo drug-mediated cytotoxicity. 
Selected compositions for gastric epithelial organoid culture recipe by Lab-A-Porter
Xeno-free (animal origin-free) hydrogel system for organoid culture
- Busslinger, Georg A et al. “The potential and challenges of patient-derived organoids in guiding the multimodality treatment of upper gastrointestinal malignancies.” Open biologyvol. 10,4 (2020): 190274. doi:10.1098/rsob.190274
- Seidlitz, Therese et al. “Gastric organoids-an in vitro model system for the study of gastric development and road to personalized medicine.” Cell death and differentiation vol. 28,1 (2021): 68-83. doi:10.1038/s41418-020-00662-2
- Alzeeb, George et al. “Three-Dimensional Culture Systems in Gastric Cancer Research.” Cancersvol. 12,10 2800. 29 Sep. 2020, doi:10.3390/cancers12102800
- Lo, Yuan-Hung et al. “A CRISPR/Cas9-Engineered ARID1A-Deficient Human Gastric Cancer Organoid Model Reveals Essential and Nonessential Modes of Oncogenic Transformation.” Cancer discovery vol. 11,6 (2021): 1562-1581. doi:10.1158/2159-8290.CD-20-1109
- Xu, Hanxiao et al. “Organoid technology in disease modelling, drug development, personalized treatment and regeneration medicine.” Experimental hematology & oncology vol. 7 30. 5 Dec. 2018, doi:10.1186/s40164-018-0122-9
Our xeno-free hydrogel system (VitroGel®) can closely mimic the natural extracellular matrix and open the door to clinical applications for 3D organoid models. Cells from different sources such as patient-derived cells can be cultured with our system with full lab automation potential for personalized 3D cell models, including highly complicated organoid models and co-culture systems.
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