Caption: This “spooky” video ends with a scientific image of intestinal crypts (blue and green) plus organoids made from cultured crypt stem cells (pink).
As Halloween approaches, some of you might be thinking about cueing up the old TV series “Tales from the Crypt” and diving into its Vault of Horror for a few hours. But today I’d like to share the story of a quite different and not nearly so scary kind of crypt: the crypts of Lieberkühn, more commonly called intestinal crypts.
This confocal micrograph depicts a row of such crypts (marked in blue and green) lining a mouse colon. In mice, as well as in humans, the intestines contain millions of crypts, each of which has about a half-dozen stem cells at its base that are capable of regenerating the various types of tissues that make up these tiny glands. What makes my tale of the crypt particularly interesting are the oval structures (pink), which are organoids that have been engineered from cultured crypt stem cells and then transplanted into a mouse model. If you look at the organoids closely, you’ll see Paneth cells (aqua blue), which are immune cells that support the stem cells and protect the intestines from bacterial invasion.
A winner in the 2016 “Image Awards” at the Koch Institute Public Galleries, Massachusetts Institute of Technology (MIT), Cambridge, this image was snapped by Jatin Roper, a physician-scientist in the lab of Omer Yilmaz, with the help of his MIT collaborator Tuomas Tammela. Roper and his colleagues have been making crypt organoids for a few years by placing the stem cells in a special 3D chamber, where they are bathed with the right protein growth factors at the right time to spur them to differentiate into the various types of cells found in a crypt.
Once the organoids are developmentally complete, Roper can inject them into mice and watch them take up residence. Then he can begin planning experiments.
For example, Roper’s group is now considering using the organoids to examine how high-fat and low-calorie diets affect intestinal function in mice. Another possibility is to use similar organoids to monitor the effect of aging on the colon or to test which of a wide array of targeted therapies might work best for a particular individual with colon cancer.
Video: Gut Reaction (Jatin Roper)
Jatin Roper (Tufts Medical Center, Boston)
Omer Yilmaz (Massachusetts Institute of Technology, Cambridge)
NIH Support: National Cancer Institute; National Institute on Aging
Tags: art, BioArt, colon, colon cancer, crypts, crypts of Lieberkühn, diet, high-fat diet, intestinal crypts, intestine, low-calorie diet, organoids, Paneth cells, stem cells, The Koch Institute Galleries
When Nancy Allbritton was a child in Marksville, LA, she designed and built her own rabbit hutches. She also once took apart an old TV set to investigate the cathode ray tube inside before turning the wooden frame that housed the TV into a bookcase, which, by the way, she still has. Allbritton’s natural curiosity for how things work later inspired her to earn advanced degrees in medicine, medical engineering, and medical physics, while also honing her skills in cell biology and analytical chemistry.
Now, Allbritton applies her wide-ranging research background to design cutting-edge technologies in her lab at the University of North Carolina, Chapel Hill. In one of her boldest challenges yet, supported by a 2015 NIH Director’s Transformative Research Award, Allbritton and a multidisciplinary team of collaborators have set out to engineer a functional model of a large intestine, or colon, on a microfabricated chip about the size of a dime.
Tags: 2015 NIH Director’s Transformative Research Award, bioengineering, colon, colon on a chip, crypts, diet, digestion, gastrointestinal disease, gastrointestinal tract, genomics, hydrogel, immunity, intestinal crypt, intestine, large intestine, microbiome, organoids, regenerative medicine, simulacrum, stem cell technology, stem cells, tissue chips
Clostridium difficile, or more commonly “C. diff,” is a nasty bacterium that claims the lives of 14,000 Americans every year. Most at risk are people with conditions requiring prolonged use of antibiotics, which have the unfortunate side effect of wiping out the natural, good bacteria in the colon—thus allowing bad bugs like C. diff to multiply unchecked. In many folks, C. diff infection can be treated by halting the original antibiotics and switching to other types of antibiotics. But for some people, that doesn’t work—C. diff is either resistant to treatment or makes a hasty comeback.
What’s to be done then? Well, researchers have known for some time that taking microbe-rich stool samples from healthy people and transplanting them into C. diff patients helps to improve their symptoms. The challenge has been figuring out a safe and effective way to do this that is acceptable to patients and doesn’t involve invasive procedures, such as colonoscopy or nasogastric tubes [1,2]. Could there be a simple solution? To put it more bluntly: what about poop pills?