NOV 23, 2016 05:07 PM PST

Engineered Intestinal Tissue With Functional Nerves Advances Research

WRITTEN BY: Carmen Leitch
Reporting in Nature Medicine, researchers have been able to use stem cells to make intestinal organoids with functional nerves. This research paves the way for advancement in both the research and treatment of Hirschsprung’s disease, a serious intestinal nerve disorder. The authors believe the work will aid medical science in using pluripotent stem cells as a therapy in regenerative medicine and organ transplantation. The research is outlined in the following video.
 

 
 "One day this technology will allow us to grow a section of healthy intestine for transplant into a patient, but the ability to use it now to test and ask countless new questions will help human health to the greatest extent," said the co-lead study investigator Michael Helmrath, MD, surgical director of the Intestinal Rehabilitation Program at Cincinnati Children's Hospital Medical Center.
 
The investigation of disease mechanism at the molecular level is aided tremendously by the use of a functional, three-dimensional model, especially one that can be tailored to a specific patient. This technology allows researchers to create such models from cells taken from individual patients and test therapeutics there, before taking them to clinical trials in people.
 
 "Many oral medications give you diarrhea, cramps and impair intestinal motility. A fairly immediate goal for this technology that would help the largest number of people is as a first-pass screen for new drugs to look for off-target toxicities and prevent side effects in the intestine," explained co-lead investigator Jim Wells, PhD, director of the Pluripotent Stem Cell Facility at Cincinnati Children's.
 
Wells builds on his 2010 work that demonstrated the first creation of human intestinal organoids in a lab. The researchers started in the same way for this work. They added in another component, nerve cells, still at the embryonic stage, called neural crest cells. They then identified the right conditions under which the cells were to be added to the intestinal organoids in order to create an innervated nerve network.
 
Human intestinal organoids with enteric (intestinal) nerves generated in a petri dish using human pluripotent stem cells, which can become any cell type in the body. / Credit: Cincinnati Children's

"We tried a few different approaches largely based on the hypothesis that, if you put the right cells together at the right time in the petri dish, they'll know what do to. It was a longshot, but it worked," said Wells. The right mix resulted in intestines and enteric nerve precursor cells growing together in a way that was similar to the development of the intestine in the fetus.
 
To determine how these organoids grew and functioned, they had to be transplanted into a live animal; for this the researchers utilized mice with suppressed immune systems. The tissues performed very well, with robust growth, nutrient processing and peristalsis – wavy muscle contractions that push food down the digestive tract.
 
The researchers also used this remarkable model to study the progression of Hirschsprung's disease, a developmental disorder in which the colon and rectum don’t have a functional nervous system, resulting in the buildup of waste. When a mutation causative for Hirschsprung’s in the gene PHOX2B was used with the model, serious problems were indeed seen in the intestinal tissues.
 
Wells and Helmrath suggested that the manufacure of this type of functional human intestine in the lab opens up an array of new opportunities. It will now be possible to conduct more in-depth research of many subjects like nutritional health, diabetes, severe intestinal diseases, and the biochemical consequences of gastric bypass surgery.
 
Sources: AAAS/Eurekalert! via Cincinnati Children's Hospital Medical Center, Nature Medicine
 
About the Author
  • Experienced research scientist and technical expert with authorships on 28 peer-reviewed publications, traveler to over 60 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
OCT 22, 2018
Videos
OCT 22, 2018
Mad Cow Disease Identified in Scottish Cow
Stringent detection systems appear to be working, but cases still happen....
NOV 05, 2018
Videos
NOV 05, 2018
The Mechanisms Underlying the Deadly Blow of the Mantis Shrimp
The mantis shrimp packs a powerful punch that can strike its enemies with one of the fastest moves in the animal kingdom....
NOV 19, 2018
Neuroscience
NOV 19, 2018
Researchers identify neural pathways that control behavioral responses to noxious stimuli
Behavioral responses to the pain perception could range from reflexive withdrawal to more complex behaviors to avoid or decrease the pain. Neurons in the lateral division of the parabrachial...
NOV 21, 2018
Cell & Molecular Biology
NOV 21, 2018
Preventing the Wrong Cells From Forming in Organoids
Organoids are advancing research by providing scientists with a 3D model of a human organ. But are they what they seem?...
NOV 24, 2018
Genetics & Genomics
NOV 24, 2018
How Fish can Teach us About Mending a Broken Heart
Our world hosts some incredible organisms, some of which might help people create treatments for disease....
DEC 03, 2018
Genetics & Genomics
DEC 03, 2018
Reducing the Potential for Negative Side Effects in CRISPR
CRISPR-Cas9 is an amazing gene-editing tool, but there are some drawbacks. This work aims to fix that....
Loading Comments...