Lab-developed intestinal organoids form mature human tissue in mice

Researchers have successfully transplanted "organoids" of functioning human intestinal tissue grown from pluripotent stem cells in a lab dish into mice -- creating an unprecedented model for studying diseases of the intestine.

Reporting their results Oct. 19 online in Nature Medicine, scientists from Cincinnati Children's Hospital Medical Center said that, through additional translational research the findings could eventually lead to bioengineering personalized human intestinal tissue to treat gastrointestinal diseases.

"These studies support the concept that patient-specific cells can be used to grow intestine," said Michael Helmrath, MD, MS, lead investigator and surgical director of the Intestinal Rehabilitation Program at Cincinnati Children's. "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."

The scientists used induced pluripotent stem cells (iPSCs) -- which can become any tissue type in the body -- to generate the intestinal organoids. The team converted adult cells drawn from skin and blood samples into "blank" iPSCs, then placed the stem cells into a specific molecular cocktail so they would form intestinal organoids.

The human organoids were then engrafted into the capsule of the kidney of a mouse, providing a necessary blood supply that allowed the organoid cells to grow into fully mature human intestinal tissue. The researchers noted that this step represents a major sign of progress for a line of regenerative medicine that scientists worldwide have been working for several years to develop.

Mice used in the study were genetically engineered so their immune systems would accept the introduction of human tissues. The grafting procedure required delicate surgery at a microscopic level, according to researchers. But once attached to a mouse's kidney, the study found that the cells grow and multiply on their own. Each mouse in the study produced significant amounts of fully functional, fully human intestine.

"The mucosal lining contains all the differentiated cells and continuously renews itself by proliferation of intestinal stem cells. In addition, the mucosa develops both absorptive and digestive ability that was not evident in the culture dish," Helmrath said. "Importantly, the muscle layers of the intestine also develop."

What This Means for Patients

The new findings eventually could be good news for people born with genetic defects affecting their digestive systems or people who have lost intestinal function from cancer, as well as Crohn's disease and other related inflammatory bowel diseases (IBD).

One of the advantages of using tissue generated from iPSCs is that the treatment process would involve the patient's own tissue, thus eliminating the risk and expense of life-long medications to prevent transplant rejection.

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Lab-developed intestinal organoids form mature human tissue in mice