For the first time, researchers growing functioning intestinal tissue from human stem cells have successfully transplanted these so-called “organoids” into mice. Once within their mouse host, the lab-grown intestinal precursors grew into mature human tissue capable of both absorbing and digesting. The work was published in Nature Medicine this week.
A human-mouse model of the small intestine would not only help us understand gastrointestinal diseases, it would also help test new treatments for these disorders. One day, this breakthrough could also help grow tissue to replace damaged organs using the patient’s own cells.
First, a team led by Michael Helmrath of the Cincinnati Children’s Hospital Medical Center converted adult cells (taken from skin and blood samples) into “blank” induced pluripotent stem cells (iPSCs), which have the potential to develop into any type of tissue in the body. A specific molecular cocktail coaxed the stem cells to differentiate into intestinal organoids.
Next, the team grafted the organoids into the kidney capsules of mice who were genetically engineered so their immune systems would accept human tissue. The placement also provided the necessary blood supply to help organoid cells grow into fully mature tissue. Once the lab-grown organoids were attached to the mouse kidney, the cells grew and multiplied on their own, and the tissue matured much further than they did in a petri dish.
After several weeks, the tissue developed into a complex structure resembling the human small intestine, complete with crypts and villi—the glands and projections of the lining that are characteristic of our small bowels. The tissue contained several different intestinal cell types (pictured to the right) and even exhibited digestive functions, such as absorption of particles into the mouse’s bloodstream and digestive enzyme activity.
After they surgically removed portions of the intestine, the researchers observed growth and adaptation of the implanted tissue—suggesting that the human intestinal tissue responded to signals released into the circulation of the mouse.
“These studies support the concept that patient-specific cells can be used to grow intestine,” Helmrath says in a news release. “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.”
Images: Helmrath lab