Human intestinal organoids grown in mice could help personalize treatments

Screen shot of human intestine grown from a single cell taken from one patient--Courtesy of Cincinnati Children's Hospital

Researchers at Cincinnati Children's Hospital have grown human intestinal tissue from pluripotent stem cells and transplanted the living tissue into mice. A potentially huge step for regenerative medicine, these so-called organoids could provide a more accurate model for testing drugs designed to work on the intestines as well as help generate intestinal tissue for new treatments.

Using adult cells drawn from skin and blood samples, scientists wiped the cells' biological memory, turning them into induced pluripotent stem cells, or iPSCs, which have the ability to differentiate into any tissue type in the body. Then, the cells were fed a specific molecular cocktail that would coax them into forming intestinal organoids.

Investigators grafted the human organoids into a mouse's renal capsule--a tough layer of fibrous connective tissue that surrounds each kidney. The mice used in the study were genetically engineered so their immune systems would not reject the new human tissues. Once attached to the kidney, the transplanted cells grew and multiplied on their own, developing into fully mature human intestinal tissue. Each mouse in the study was able to produce significant amounts of fully functional human intestinal tissue.

Described online Oct. 19 in Nature Medicine, the research could eventually lead to bioengineering personalized human intestinal tissue to treat gastrointestinal diseases caused by genetic defects as well as cancer, Crohn's disease and other related inflammatory bowel diseases.

"These studies support the concept that patient-specific cells can be used to grow intestine," said Dr. Michael Helmrath, lead investigator and surgical director of the Intestinal Rehabilitation Program at Cincinnati Children's, in a statement. "This provides a new way to study the many diseases and conditions that can cause intestinal failure, from genetic disorders appearing at birth to conditions that strike later in life, such as cancer and Crohn's disease. These studies also advance the longer-term goal of growing tissues that can replace damaged human intestine."

Tissue generated from iPSCs is an attractive option for regenerative medicine because the therapies involve the patient's own tissue, eliminating the risk of a patient's immune system rejecting transplanted tissue. Patients that have undergone organ transplants must take immunosuppressant drugs for the rest of their lives to keep the transplanted organ from being rejected.

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