Researchers from Cincinnati Children’s Hospital Medical Center have used induced pluripotent stem cells to grow “organoids” of fully functioning human intestines. Having successfully transplanted these organoids into mice, the team says their findings could one day lead to the creation of personalized human intestinal tissue for the treatment of gastrointestinal diseases.
Researchers say the development of fully functional intestinal organoids could lead to personalized treatments for gastrointestinal diseases.
The Cincinnati Children’s team, led by Dr. Michael Helmrath, surgical director of the Intestinal Rehabilitation Program at the hospital, publish their findings in the journal Nature Medicine.
Drawn from adult cells, induced pluripotent stem cells (iPSCs) have the ability to change into any type of body tissue. In this study, Dr. Helmrath and his team used human adult cells from skin and blood samples to develop “blank” iPSCs. The researchers then added the iPSCs to a distinct “molecular cocktail” that encouraged them to turn into intestinal organoids – miniature structures that resemble intestines.
The team then transplanted the organoids into the kidneys of mice with genetically modified immune systems that allowed them to accept human tissues. The organoids were able to gain the optimal amount of blood to develop into mature human intestinal tissue.
According to the researchers, each mouse produced high levels of fully functional human intestinal tissue. The organoids grew and multiplied by themselves once they were attached to the kidneys.
“The mucosal lining contains all the differentiated cells and continuously renews itself by proliferation of intestinal stem cells,” says Dr. Helmrath. “In addition, the mucosa develops both absorptive and digestive ability that was not evident in the culture dish. Importantly, the muscle layers of the intestine also develop.”
Potential to eliminate lifelong medication and transplant rejection
The researchers say these findings could pave the way for personalized treatments for individuals with gastrointestinal disorders or reduced digestive function as a result of other conditions.
A patient’s own cells could be used to create intestinal tissue, which could then be transplanted. This could potentially prevent transplant rejection and eliminate the need for lifelong medications.
Commenting on the findings, Dr. Helmrath says:
“This study supports the concept that patient-specific cells can be used to grow intestine. 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 researchers stress, however, that it will be many years before this concept is used in medical practice.
But they note that it could have immediate benefits, such as boosting the development of new drugs. Organoids developed in laboratories could replace the need for animal models bred to mimic human disease. Testing in these models often presents problems; some drugs that are effective in mice, for example, may not be effective in humans.
The researchers say that having the ability to test drugs in models of human organs “could shave years” off the drug development process.