Engineers Grow Pancreatic 'Organoids' That Mimic the Real Thing

Researchers from MIT have developed a new way to grow tiny replicas of the pancreas, using either healthy or cancerous pancreatic cells. They believe that their 'specialized gel' could also be useful for studying lung, colorectal, and other cancers, including how potential cancer drugs affect tumors and their environment. The findings have been published in the journal Nature Materials. MIT reports: Using a specialized gel that mimics the extracellular environment surrounding the pancreas, the researchers were able to grow pancreatic 'organoids,' allowing them to study the important interactions between pancreatic tumors and their environment. Unlike some of the gels now used to grow tissue, the new MIT gel is completely synthetic, easy to assemble and can be produced with a consistent composition every time. The researchers have also shown that their new gel can be used to grow other types of tissue, including intestinal and endometrial tissue. About 10 years ago, [Linda Griffith, the School of Engineering Professor of Teaching Innovation and a professor of biological engineering and mechanical engineering, and her lab] started to work on designing a synthetic gel that could be used to grow epithelial cells, which form the sheets that line most organs, along with other supportive cells.

The gel they developed is based on polyethylene glycol (PEG), a polymer that is often used for medical applications because it doesn't interact with living cells. By studying the biochemical and biophysical properties of the extracellular matrix, which surrounds organs in the body, the researchers were able to identify features they could incorporate into the PEG gel to help cells grow in it. One key feature is the presence of molecules called peptide ligands, which interact with cell surface proteins called integrins. The sticky binding between ligands and integrins allows cells to adhere to the gel and form organoids. The researchers found that incorporating small synthetic peptides derived from fibronectin and collagen in their gels allowed them to grow a variety of epithelial tissues, including intestinal tissue. They showed that supportive cells called stromal cells, along with immune cells, can also thrive in this environment.

In the new study, Griffith and [Claus Jorgensen, a group leader at the Cancer Research UK Manchester Institute] wanted to see if the gel could also be used to support the growth of normal pancreatic organoids and pancreatic tumors. Traditionally, it has been difficult to grow pancreatic tissue in a manner that replicates both the cancerous cells and the supporting environment, because once pancreatic tumor cells are removed from the body, they lose their distinctive cancerous traits. Griffith's lab developed a protocol to produce the new gel, and then teamed up with Jorgensen's lab, which studies the biology of pancreatic cancer, to test it. Jorgensen and his students were able to produce the gel and use it to grow pancreatic organoids, using healthy or cancerous pancreatic cells derived from mice. 'We got the protocol from Linda and we got the reagents in, and then it just worked,' Jorgensen says. 'I think that speaks volumes of how robust the system is and how easy it is to implement in the lab.'

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