Lab-Grown Intestinal Tissue Regenerates Gut Lining in Dogs

Over the last five years considerable progress has been made in the tissue engineering of intestines. Researchers have created sections of intestine, grown intestine organoids, and regenerated damage to intestines in laboratory animals. Here is the latest example:

Working with gut stem cells from humans and mice, scientists have successfully grown healthy intestine atop a 3-D scaffold made of a substance used in surgical sutures. The tube-shaped scaffold was a big first step on the quest to develop an implantable replacement intestine. But the new work pushes that effort further because it shows 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. Researchers caution that a fully functioning replacement intestine for humans is far off, but they say their results have laid the critical groundwork to do so. "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."

In an initial set of experiments researchers took stem cells from the colons of babies undergoing intestinal surgeries and from mice, then 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, the scientists say, was to create a mixture that closely mimics the natural composition of the gut. 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.

Next, 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 say, 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 didn't get intestinal implants experienced continued inflammation and scarring of their guts.

Link: http://www.hopkinsmedicine.org/news/media/releases/lab_grown_3_d_intestine_regenerates_gut_lining_in_dogs

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