A new 3D “organoid” culture system for growing both normal and cancerous pancreatic cells in the lab promises to transform research on pancreatic cancer and the development of new personalized treatments.
The researchers report how they used the new organoid technique to grow pancreatic tissue from cells isolated from lab mice and human patients in the journal Cell.
There is a desperate need for radical new approaches in the fight against pancreatic cancer – a deadly disease where only 6% of patients live more than 5 years after diagnosis. It is notoriously difficult to spot pancreatic cancer in the early stages and most cases are only diagnosed after it has started to spread.
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The new study is a significant step forward, as David Tuveson, co-leader of the study and professor at Cold Spring Harbor Laboratory (CSHL), NY, and Director of Research for The Lustgarten Foundation, NY, notes:
“With this development, we are now able to culture both mouse and human organoids, providing a very powerful tool in our fight against pancreatic cancer.”
The new organoid technique means researchers will be able to examine what happens at the molecular level to drive the disease and look for new drug targets.
To study a disease like cancer – which develops when cells malfunction and spread – you need a steady supply of normal and cancerous cells that can be grown in the lab.
But normal and cancerous pancreatic cells are extremely difficult to grow in the lab. This is further complicated by the fact the cancer arises in pancreatic ductal cells – which account for only around 10% of the cells in the organ – making it hard to track the small, cell-level changes that accompany tumor progression.
Because of these difficulties, researchers tend to use genetically engineered mice rather than tissue cultures to study pancreatic cancer in the lab. But it can take up to a year to breed the number and type of mice required for a particular investigation.
The potential to use organoids is a game changer for pancreatic cancer research. It means researchers can grow 3D tissue made entirely of ductal cells, uncontaminated by the other types of cell that normally accompany them when retrieved from samples.
The organoids grow as 3D hollow spheres in a gel-like complex filled with growth-inducing factors and connecting fibers. When the organoids are big enough, they can be transplanted into mice, where they develop fully into pancreatic cancer.
Co-lead author Dr. Chang-Il Hwang, who works in Prof. Tuveson’s group at CSHL, says, “We now have a model for each stage in the progression of the disease.”
Another advantage the new technique brings is to broaden the scope of patients from whom pancreatic tissue can be obtained.
Currently, researchers have limited access to patient samples, which can only be obtained during surgery or autopsy. However, only around 15% of pancreatic cancer patients are eligible for surgery by the time they are diagnosed – either because the disease is too advanced, or because the tumor is entwined in critical blood vessels.
But the new technique the study describes allows scientists to grow organoids from material obtained in biopsies which are used to diagnose pancreatic cancer.
Thus the study shows there is a way to grow 3D tissue in the form of organoids relatively quickly from any pancreatic cancer patient, offering the potential to study the disease in a much wider population.
The team is now working with the National Cancer Institute to build a repository of pancreatic tumor samples that they hope to make available to all pancreatic cancer researchers.
In October 2014, Medical News Today reported another study where researchers grew fully functional organoids of human intestines and successfully transplanted them into mice. The team in that study – from Cincinnati Children’s Hospital Medical Center – also hopes the technique means we will eventually be able to grow personalized human tissue, in their case for the treatment of gastrointestinal diseases.