Tissue Replicas Studied for Clues to IBD

If Stephan Targan, MD, has his way, a series of diminutive intestines growing in petri dishes will eventually lead to a revolutionary new way to study and treat inflammatory bowel disease (IBD). About 1 million Americans suffer from IBD, a term that covers a group of conditions – including ulcerative colitis and Crohn's disease – associated with multiple complications such as intestinal failure, growth impairment, cancer and early death.

With rates of IBD rising steadily, Targan has made Cedars-Sinai one of the world's leading IBD centers and has been exploring ways to improve on current therapies, which are limited to antibiotics, corticosteroids and immune modifying agents – all of which come with serious side effects over the long term. But what if he could actually re-create his patients' guts in the lab dish and study them? Enter Clive Svendsen, PhD, and the Cedars-Sinai Regenerative Medicine Institute – and the start of a very fruitful collaboration.

Harnessing the power of induced pluripotent stem cells, Targan's group – led by Robert Barrett, PhD – has teamed up with Svendsen and other colleagues at the Regenerative Medicine Institute to successfully create intestine replicas in the lab. Here's how it works: First, adult skin cells are taken from patients. Second, the cells are reprogrammed to a primitive stem cell state and then developed into three-dimensional intestine replicas – so-called organoids – in the lab.

"Our aim is to regenerate selected abnormalities seen in patients' intestinal tissue, such as leaky intestinal barrier, but in the lab dish," explained Targan, who is the director of the Cedars-Sinai F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute. "Stem cells represent such a tremendous boon because they let us recreate the problem right in the lab, and because we may one day be able to transplant healthy cells to repair the organs."

"There are no clinical trials on this yet, and we don't have all the answers," Svendsen said, "But there is no doubt we're on the threshold of a radically new era in regenerative medicine and that IBD research should be one of its major beneficiaries. What we're able to consider today would have been unthinkable a decade ago."

Photos from top: Stephan Targan, MD; Fluorescent microscopy images show that intestinal organoids, created by Cedars-Sinai researchers, have cell types typically found in the intestines.