Lab-grown 3D intestine regenerates gut lining in dogs

Scientists have regenerated gut tissue in the colons of dogs with missing gut lining using a lab grown 3D intestine, an advance that could lead to the development of an implantable replacement intestine for humans.

The technique could help treat a range of devastating disorders - including infections, cancer and trauma - that result in loss or death of gut tissue, researchers said. Chief among them is a condition that affects 12% of premature newborns, called necrotising enterocolitis (NEC), which is marked by the rapid death of intestinal cells and permanent loss of intestinal tissue.

"Our experiments show that the architecture and function of our lab-made intestine strikingly resemble those of the healthy human gut, giving us real hope that our model could be used as the backbone for replacement intestine," said principal investigator David Hackam, surgeon-in-chief at the Johns Hopkins Children's Centre. In an initial set of experiments, researchers took stem cells from the colons of babies and mice, and added immune cells called macrophages, the body's scavengers that seek out and engulf debris along with foreign and diseased cells.

To this mix, they added cells called fibroblasts, whose function is to form collagen and other connective substances that bind tissues and organs together. The idea was to create a mixture that closely mimics the natural composition of the gut, researchers said. Adding these components enhanced the growth of intestinal stem cells and differentiation into various mature cell types critical to the function of a healthy intestine, they said.

In another set of experiments, researchers added probiotic bacteria to the newly created intestinal tissue. Doing so further amplified the growth and differentiation of new gut cells, specifically the growth of Paneth cells responsible for production of infection-fighting proteins that guard against intestinal infections, a finding that highlights the therapeutic potential of certain probiotics for NEC, Hackam said.

The researchers implanted the newly created intestine into the bellies of mice. In a matter of days, the implanted intestine began producing new intestinal stem cells and stimulated the growth of new blood vessels around the implant. That observation, researchers said, affirmed the ability of the 3D intestine to spur the growth of new tissue not only in lab dishes, but also in living organisms.

In a final step, the researchers implanted pieces of the newly created intestine - about 1.6 inches in length - into the lower portion of dog colons lacking parts of their intestinal lining. For two months, the dogs underwent periodic colonoscopies and intestinal biopsies. The guts of dogs with implanted intestines healed completely within eight weeks.

The study appears in the journal Regenerative Medicine.