29 April 2021

3D organoids of the pancreas

The first 3D organoid model of the human pancreas has been created

Tatiana Matveeva, "Scientific Russia"

Scientists from the Beth Israel Medical Center Cancer Research Institute (BIDMC) have successfully created the first three-dimensional models of pancreatic organoids from human stem cells. It is expected that this platform will help to study more deeply the origin and development of pancreatic cancer, as well as help to find markers for early diagnosis and monitoring of the disease, the BIDMC press service reports. A detailed description of the research platform appeared in the journal Cell Stem Cell (Huang et al., Commitment and oncogene-induced plasticity of human stem cell-derived pancreatic acinar and ductal organoids).

The pancreas is a hormone–producing organ consisting of ducts and structures of acinar cells. Researchers suspect that one of the most common types of pancreatic cancer (ductal adenocarcinoma of the pancreas) occurs in the cells lining the acinar and ductal structures. However, until now, scientists have not been able to successfully grow and maintain human acinar structures in the laboratory, which called into question their ability to test the hypothesis on a model.

Unlike previous platforms for studying pancreatic cancer, this first-of-its-kind organoid model includes both acinar and ductal structures, which play a crucial role in most cases of pancreatic cancer.

In order to make stem cells turn into ductal and acinar cells, scientists methodically tested various combinations of cell growth media used for different periods of time. The culmination of more than five years of work presented in the study represents the first time that researchers have successfully generated human acinar cells in culture and maintained them long enough to be used in experiments.

Then the scientists used two separate lines of ductal and acinar organoids, constructed with the inclusion of gene mutations that are associated with pancreatic cancer. When the organoids were later implanted into mice, different clones behaved differently and predictably. For example, one mutation caused seven out of 10 mice to have acinar-like organoids transplanted, cellular changes similar to early pancreatic cancer in humans.

Understanding the mechanisms that regulate these events will help scientists in the future to figure out how pancreatic cancer occurs and identify it at an early stage. 

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