Engineers grow pancreatic ‘organoids’ that mimic the real thing

Studying these organoids could help researchers develop and test new treatments for pancreatic cancer, one of the deadliest types of cancer

Science Daily

MIT engineers have discovered a novel method to manufacture miniature copies of the pancreas using healthy or malignant pancreatic cells. Their new models may help researchers design and test medicines for pancreatic cancer, one of the most difficult to cure. The researchers grew pancreatic “organoids” in a gel that mimicked the extracellular environment surrounding the pancreas, enabling them to investigate key interactions between pancreatic cancers and their surroundings. Unlike other current tissue-growing gels, the new MIT gel is entirely synthetic, simple to build, and reproducible.
“Reproducibility is a significant problem,” says Linda Griffith, professor of biological and mechanical engineering at the School of Engineering. It’s important to manage the microenvironment while growing these organoids, according to the scientific community. The researchers have also demonstrated that their novel gel can develop intestinal and endometrial tissue. The study is co-authored by Griffith and Claus Jorgensen, a group leader at the Cancer Research UK Manchester Institute. The main author is Christopher Below, a former CRUK Manchester Institute graduate student.

Traditionally, laboratories have grown organoids in a plate using commercial tissue-derived gel. The most commonly used commercial gel, however, is a complicated combination of proteins, proteoglycans, and growth factors generated from a mouse tumor, Griffith explains. It also doesn’t always allow for multicellular development. Griffith’s lab began working on a synthetic gel to produce epithelial cells, which form the sheets that coat most organs, and other supporting cells around ten years ago.

The gel they created uses polyethylene glycol (PEG), a non-toxic polymer that doesn’t interact with live cells. The researchers identified characteristics they might include into the PEG gel to assist cells grow in it by researching the extracellular matrix’s metabolic and physical properties. Peptide ligands interact with integrins, which are cell surface proteins. The ligand-integrin sticky binding enables cells to cling to the gel and form organoids. These tiny synthetic peptides were discovered to enable the researchers to develop a range of epithelial tissues, including intestinal tissue. They found that stromal cells, like immune cells, can flourish in this environment.

Griffith and Jorgensen sought to explore whether the gel might help normal pancreatic organoids and pancreatic cancers develop. It’s proven challenging to produce pancreatic tissue that duplicates both the malignant cells and their surroundings because once removed from the body, pancreatic tumor cells lose their dangerous characteristics.

Griffith’s group created the new gel’s technique and tested it with Jorgensen’s lab, which researches pancreatic cancer biology. Jorgensen and his students were able to generate pancreatic organoids from healthy or malignant mouse pancreatic cells. “We received the chemicals and the procedure from Linda, and everything simply worked,” Jorgensen adds. “I believe it speaks volumes about the system’s robustness and ease of use in the lab.” Some of the other methods they tested were too complex or didn’t replicate the microenvironment in live tissues. Using this gel, Jorgensen’s team discovered that pancreatic organoids express many of the same integrins as pancreatic cancers. Moreover, macrophages (an immune cell type) and fibroblasts (a supporting cell type) were able to proliferate in the microenvironment.

The gel may also be used to generate organoids from pancreatic cancer cells from patients. They think it may help research lung, colorectal, and other malignancies. It may be used to study how cancer medicines impact tumors and their surroundings. Griffith also intends to utilize the gel to produce and analyze endometriosis tissue, a disease in which the uterine lining tissue grows outside the uterus. This causes pain and infertility. The new gel is entirely synthetic and can be produced in a lab by combining certain precursors, such as PEG and polypeptides. The researchers have patented the technique and are looking to license it to a firm that might commercialize it.

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