Los Angeles,
16
February
2018
|
09:00 AM
America/Los_Angeles

Scientists Produce Human Intestinal Lining That Re-Creates Living Tissue Inside Organ-Chip

Findings Have Potential to Advance Personalized Treatments for Gastrointestinal Diseases

Investigators have demonstrated how cells of a human intestinal lining created outside an individual’s body mirror living tissue when placed inside microengineered Intestine-Chips, opening the door to personalized testing of drug treatments.

The findings have the potential to change how patients are treated for debilitating, inflammatory gastrointestinal diseases with a genetic component, such as Crohn's disease, ulcerative colitis and irritable bowel syndrome.

Instead of exposing a patient to drug treatments that may be costly, ineffective or carry harmful side effects, scientists could use the individual’s own stem cells to produce a duplicate of the intestinal lining on an Intestine-Chip and test multiple drugs on it. Scientists then could determine which drug worked best on that patient’s intestine.

The study was conducted by investigators at the Cedars-Sinai Board of Governors Regenerative Medicine Institute and Emulate Inc. in Boston.

This advance will allow biomedical scientists to study the functioning of an individual's intestinal lining in a controlled microenvironment, where the lining can interact with immune cells, blood cells and drugs, said Robert Barrett, PhD, assistant professor of Medicine and research scientist at the Regenerative Medicine Institute. Barrett is senior author of the study, published in Cellular and Molecular Gastroenterology and Hepatology, a journal of the American Gastroenterology Association.

"This pairing of biology and engineering allows us to re-create an intestinal lining that matches that of a patient with a specific intestinal disease—without performing invasive surgery to obtain a tissue sample," said Clive Svendsen, PhD, director of the Regenerative Medicine Institute and a co-author of the study. "We can produce an unlimited number of copies of this tissue and use them to evaluate potential therapies. This is an important advance in personalized medicine."

The study team used two advanced technologies to produce and sustain the intestinal lining: Cedars-Sinai provided the induced pluripotent stem cells, or iPSCs, while Emulate supplied its Intestine-Chip, which is made out of a flexible polymer that features tiny channels that can be lined with thousands of living human cells.

To make the iPSCs, Cedars-Sinai investigators first took small samples of blood and skin cells from an adult. They reprogrammed these cells into iPSCs, which are similar to embryonic stem cells and can produce any type of body cell. Using special proteins and other substances, the scientists prodded the iPSCs to produce cells of the intestinal lining. Each cell bore the unique genetic fingerprint and characteristics of the adult who donated the original cells. The new cells were used to grow miniature versions of the person's intestine lining, known as organoids.

To make the iPSCs, Cedars-Sinai investigators first took small samples of blood and skin cells from an adult. They reprogrammed these cells into iPSCs, which are similar to embryonic stem cells and can produce any type of body cell. Using special proteins and other substances, the scientists prodded the iPSCs to produce cells of the intestinal lining. Each cell bore the unique genetic fingerprint and characteristics of the adult who donated the original cells. The new cells were used to grow miniature versions of the person's intestine lining, known as organoids.