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
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- These models establish unnatural geometric and mechanical constraints by adhering cells to an artificial substrate (either plastic or glass). [3]
- Such as culture affects cell polarity and therefore, potentially, tumour phenotypes. [3]
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Transgenic animal models of gastric cancer tumorigenesis have been advanced. [3]
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- 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 [3]
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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:
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- Gastric cancer ranking as the fifth most common malignancy, the third leading cause of cancer-related deaths. [2]
- 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. [3]
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- Although treatment effectiveness has improved during the past decade, gastric cancer survival rates remain poor. [3]
- This suggests an urgent need to advance innovative therapies available to gastric cancer patients. [3]
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Patient-derived organoids biobanks provide a great advantage over classical 2D cell lines in gastric tumour research [1]
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- Nanki and colleagues have generated 37 PDO lines. [1]
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- They obtained patient-derived organoids of all gastric tumour subtypes except for the Epstein-Barr virus-associated one. [1]
- Established patient-derived organoids recapitulated the same histopathological features as the original tumour. [1]
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- Yan and colleagues have established 46 PDOs. [1]
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- They classified them into 4 gastric subtypes with comparable mutational spectra. [1]
- They observed sub-clonal tumour evolution by comparing multiple biopsies obtained from the primary tumour or even metastasis of the same patient. [1]
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- Nanki and colleagues have generated 37 PDO lines. [1]
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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 [3].
- Use human and mouse organoids for disease modelling
For example, the use of gastric organoids has facilitated many important discoveries regarding H. pylori pathogenesis [5], pediatric gastric homeostasis and pediatric mucosal diseases [6]
- 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. [1]
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- They can be rapidly established and expanded in a relatively short time for in vitro drug screening experiments, for therapy prediction and guidance. [1]
Example on limitation of current organoid research
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- Organoids only contain epithelial layers without tissue microenvironments, such as the immune system and nervous system. [5]
- Fully maturation to adult organs or tissues is a bottleneck needed to be addressed. [5]
- Dependence on the extracellular matrix or basement membrane extract of current organoids. [5]
- The culture medium needs to be further refined for the long-term expansion of some organoids. [5]
- Growth factors or molecular inhibitors in culture medium might have some effects on drug responses of organoids. [5]
Some future trends on organoid-related cancer research
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- Current data suggest a good predictive value of patient-derived organoids in drug and radiation assays, even if the overall mutational landscape is unknown.[1]
- 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. [3]
- New clinical trials are required to further validate the benefits of gastric cancer patient-derived tumour organoids in personalized medicine.[3]
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- To assess the correlation between the in vivo primary tumour response and the ex vivo drug-mediated cytotoxicity. [3]
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Selected compositions for gastric epithelial organoid culture recipe by Lab-A-Porter
EGF
FGF-10
Noggin
R-Spondin-1
Wnt-3a
Gastrin
Y 27632
A 83-01
Nicotinamide
SB 202190
Xeno-free (animal origin-free) hydrogel system for organoid culture
References:
- 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
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