A newly developed technology platform has the potential to treat diseases like diabetes, IBS, and obesity by using enteroendocrine (EE) cells found in human intestinal cells, according to a recent study. Although enteroendocrine cells make up only about 1% of intestinal cells, they produce around fifteen different hormones that play a role in regulating digestion and metabolic function.
Creating Organoids
The new organoid platform, developed at Boston Children’s Hospital, is meant to pinpoint drugs that can increase the amount of EEs and encourage them to generate more needed hormones. “There’s been interest in exploiting human intestinal stem cells and EE cells to treat disease,” says David Breault, MD, Ph.D. in a statement. Breault is associate chief of the Division of Endocrinology at Boston Children’s. “But the field is still in a nascent stage. This will open new avenues of discovery.”
Using a newly developed protocol, Daniel Zeve, MD, and David Breault, MD, have been able to derive human enteroendocrine cells from human intestinal stem cells. They are shown here growing in a 3-D intestinal organoid. (Credit: Daniel Zeve, Boston Children’s Hospital)
Together with Daniel Zeve, MD, Ph.D., the study’s chief investigator, Breault derived tissue from intestinal biopsies of patients at the children’s hospital and from adult patients at Massachusetts General Hospital. Researchers then isolated the area between intestinal villi known as the “valleys” where intestinal cells can be found. Then organoids were created from the intestinal cells to replicate the biology of the duodenum and rectum. The organoids were then used as a platform to test the effectiveness of various drugs.
“We tried a variety of small molecules with the goal of making more EE cells and/or more hormones,” says Zeve. Zeve is an attending physician in endocrinology and a member of Breault’s lab. Three chemicals were found that, when used in combination, increased the production of EE cells. The chemicals also increased the amount of six different hormones: glucose-dependent insulinotropic polypeptide (GIP), cholecystokinin, somatostatin, serotonin, glucagon-like peptide-1 (GLP-1), and peptide YY.
New Treatment Options
This new strategy is more efficient because it avoids the need for genetic techniques. Scientists have filed a U.S. patent application and hope to use the new platform for further drug testing. Breault and Zeve are keen to find FDA-approved compounds that mimic the same result as their organoids. Of particular interest is identifying an oral drug that would allow those with type 1 diabetes to make insulin, or help people with obesity lose weight by encouraging their bodies to produce the hormone GLP-1.
Despite the fact that drugs are already available that mimic the effects of GLP-1 to encourage weight loss, many of them come with unpleasant side effects such as headaches, vomiting, and nausea. Breault and Zeve also hope to investigate medications to encourage the production of cholecystokinin, GIP, and peptide YY for diabetes and weight management. “The ultimate goal would be to identify a medication that induces the secretion of multiple hormones at once,” says Zeve. “This most likely mimics what happens in the body after a meal and may prevent side effects that could occur with the overproduction of just one hormone.”
Find this study in the journal Nature Communications.
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