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Dogs with missing gut lining treated with lab-grown 3D intestine
In a major advancement towards an implantable replacement intestine for humans suffering from devastating gut diseases, researchers have successfully grown healthy intestine atop a 3-D scaffold that can function well in a living organism.
New York: In a major advancement towards an implantable replacement intestine for humans suffering from devastating gut diseases, researchers have successfully grown healthy intestine atop a 3-D scaffold that can function well in a living organism.
The laboratory-created intestine successfully regenerated gut tissue in the colons of dogs with missing gut lining, the researchers reported.
"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 Johns Hopkins Children's Centre in the US.
The experiments bring researchers closer to creating an implantable intestine as replacement therapy for a range of disorders -- including infections, cancer and trauma -- that result in loss or death of gut tissue.
The lab-grown intestine was created atop a 3-D scaffold made of a substance used in surgical stitches.
The tube-shaped scaffold, designed several years ago in collaboration with Cornell University researchers and composed of biodegradable material similar to that used in surgical stitches, was a big first step on the quest to develop an implantable replacement intestine.
But the new work pushes that effort further because it showed how stem cells, when mixed with immune and connective tissue cells, can grow into normal gut tissue around the scaffold and function inside a living mammal.
When the researchers implanted the newly-created intestine into the bellies of mice, the implanted intestine began producing new intestinal stem cells in a matter of days and stimulated the growth of new blood vessels around the implant.
That observation, researchers said, affirmed the ability of the 3-D intestine to spur the growth of new tissue not only in lab dishes, but also in living organisms.
In a final step, the investigators 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.
Strikingly, the guts of dogs with implanted intestines healed completely within eight weeks.
By contrast, dogs that did not get intestinal implants experienced continued inflammation and scarring of their guts.
"Our results move research beyond the proof-of-concept realm," study one of the study authors Stephen Badylak from University of Pittsburgh noted.
"These results demonstrate that a mixture of synthetic and natural tissue can spur the formation of new gut cells and function well in living organisms despite the presence of naturally occurring inflammation and microbes found in the living gut," Badylak said.
Researchers, however, cautioned that a fully functioning replacement intestine for humans is far off, but they said their results have laid the critical groundwork to do so.
The study was published in the journal Regenerative Medicine.