Miniature human stem-cell-derived gut grown in mice

A section of functioning human small intestine has been transplanted into mice, giving scientists a new model with which to study intestinal
diseases.

The tissue was grown from human stem cells in the lab before
being grafted onto mouse kidneys, allowing the cells to develop into functioning sections of intestine.

'These studies support the concept that patient-specific
cells can be used to grow intestine,' said Dr Michael Helmrath from Cincinnati
Children's Hospital, who led the work. '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.'

The scientists took human skin and blood samples and
reprogrammed these cells to become induced pluripotent stem (iPS) cells. By adding a
mixture of chemicals, they could then transform the iPS cells to form segments of intestinal tissue.

To provide these 'organoids' with a blood supply so they
could grow further, the tissue was placed into mouse kidney capsules: tough,
fatty membranes that protected the growing organs from damage.

The mature, transplanted organoid contained many of the types of cells
seen in the small intestine, meaning it could absorb and digest
nutrients. 'Importantly, the muscle layers of the intestine also develop,' said
Dr Helmrath. The mice used in this study were genetically engineered so
that their immune systems would not reject the human tissue.

The researchers say the study brings them closer to growing
organs for transplant using the patient's own cells, minimising the risk of
rejection. 'These studies also advance the longer-term goal of growing tissues
that can replace damaged human intestine,' said Dr Helmrath.

But in the more immediate future, the mouse model should make testing drugs
for conditions such as inflammatory bowel disease easier and faster, 'shaving
years off the drug development process', the researchers said in a press release.

The study was published in Nature Medicine.