Pancreatic Organoids

The pancreas is a mixed endocrine and exocrine gland that plays a key role in digestion and metabolic homeostasis. Pancreatic dysfunction is exemplified in many cases, including metabolic disorders (T2D), autoimmune disease (T1D), inflammation (pancreatitis), and cancer (ductal adenocarcinoma). Traditional models for studying these diseases include exocrine and endocrine cell lines as well as animals. However, these models often fail to recapitulate the complex microenvironment of the human pancreas. Cell lines cannot reflect the complex interplay of multiple cell types in the pancreas, while animal models rarely reflect human physiology. This is evidenced by the large differences in the cytoarchitecture of pancreatic islets in humans, primates and rodents. The gene expression patterns in specific cells vary across species, directly affecting their response to treatment. These support the need for an artificial system that can recapitulate the complex cellular structure of the pancreas.

Recent breakthroughs in three-dimensional (3D) culture methods have led to the development of organoid culture platforms, which allow researchers to perform translation studies on long-term in vitro cultures that are not limited by obstacles present in 2D culture or animal models.

Organoids represent an important step in the functional in vitro modeling of the pancreatic tissue. Although the expansion and differentiation protocols are still being improved, studies using human pancreatic organoids have increased our understanding of pancreatic development, homeostasis, and benign and malignant pancreatic diseases. Current applications of pancreatic organoid technology include research on tissue regeneration, disease modeling, and drug screening.

At OrganoLab, we have established 3D culture conditions in Matrigel to effectively expand the dissociated pancreatic progenitor cells. By manipulating the composition of the medium, we can generate either hollow spheres mainly composed of pancreatic progenitors, or complex organoids that spontaneously undergo pancreatic morphogenesis and differentiation. For more details, please feel free to contact us.

References

1. Hohwieler M. et al.; Human pluripotent stem cell-derived acinar/ductal organoids generate human pancreas upon orthotopic transplantation and allow disease modelling. Gut, 2017, 66: 473-486.
2. Wills, E. S. et al.; Building pancreatic organoids to aid drug development. Gut, 2017, 66(3): 393-394.
3. Georgakopoulos, N. et al.; Long-term expansion, genomic stability and in vivo safety of adult human pancreas organoids. BMC Developmental Biology, 2020, 20(1): 4.
4. Greggio, C. et al.; Artificial three-dimensional niches deconstruct pancreas development in vitro. Development, 2013, 140(21): 4452-4462.
5. Qadir, M. M. F. et al.; Development of bioartificial pancreas/pancreas organoids. Encyclopedia of Tissue Engineering and Regenerative Medicine, 2019, 1-3: 209-216.
6. Balak, J. R. A. et al.; Organoids from the Human Fetal and Adult Pancreas. Current Diabetes Reports, 2019, 19(12): 160.