Engineers grow pancreatic organoids that mimic the real thing

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"MIT engineers, in collaboration with scientists at Cancer Research UK Manchester Institute, have developed a new way to grow tiny replicas of the pancreas, using either healthy or cancerous pancreatic cells. Their new models could help researchers develop and test potential drugs for pancreatic cancer, which is currently one of the most difficult types of cancer to treat.
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. ...

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. ..."

"... Altered tissue stiffness—a hallmark of pancreatic cancer—was recapitulated in culture by adjusting the hydrogel properties to engage mechano-sensing pathways and alter organoid growth. Pancreatic stromal cells were readily incorporated into the hydrogels and replicated phenotypic traits characteristic of the tumour environment in vivo. This model therefore recapitulates a pathologically remodelled tumour microenvironment for studies of normal and pancreatic cancer cells in vitro."

Engineers grow pancreatic “organoids” that mimic the real thing | MIT News | Massachusetts Institute of Technology Studying these organoids could help researchers develop and test new treatments for pancreatic cancer, one of the deadliest types of cancer.

A microenvironment-inspired synthetic three-dimensional model for pancreatic ductal adenocarcinoma organoids (no public access)

MIT and Cancer Research UK Manchester Institute researchers have developed a synthetic gel that can be used to grow tiny pancreatic organoids, seen here, from human pancreatic cells.