CHOP researchers develop novel approach to capture hard-to-view portion of colon in 3D

February 27, 2020

Philadelphia, February 27, 2020 - In a groundbreaking discovery, researchers at Children's Hospital of Philadelphia (CHOP) developed a new imaging method that allows scientists to view the enteric nervous system (ENS) - a key part of the human colon - in three dimensions by making other colon cells that normally block it invisible. The ENS has previously only been visible in thin tissue slices that provide limited clinical information. The findings were published online today in the journal Gastroenterology.

The ENS regulates many key functions of the bowel, such as the movement of food and nutrients, secretion of fluid, repair of the bowel lining and control of blood flow. Because the ENS has many nerve cell types that allow it to respond to changing conditions within the bowel independent of the brain or spinal cord, the ENS is sometimes called the body's "second brain."

The ENS is difficult to see with conventional imaging methods because it is buried within the bowel wall. Defects in the ENS cause Hirschsprung disease, a birth defect that requires surgical intervention, as well as other conditions in which food is unable to move properly through the bowel. ENS defects may also contribute to common problems like irritable bowel syndrome (IBS).

"Having three-dimensional images of the colon enteric nervous system provides us with new insight into the cells that control bowel function and may help us better understand disorders of the colon," said Robert Heuckeroth, MD, PhD, a pediatric gastroenterologist in the Division of Gastroenterology, Hepatology and Nutrition at CHOP, Research Director and Norman and Irma Braman Endowed Chair of CHOP's Lustgarten Center for GI Motility and senior author of the study. "To do this work, we had to invent a new way to make the colon invisible, stain the cells we were interested in seeing and generate thousands of images."

Using mouse and human colon tissues, the study team developed an imaging method that combined several techniques, including tissue and cell staining, the use of pinhole microscopes and quantitative analysis to characterize the cells of the colon in three dimensions. By not sectioning tissue, this new approach preserves the associations with other bowel cells in three-dimensional space. This is important in assessing bowel motility, which requires many cell types to work together to coordinate muscle contration and relaxation.

In total, the study team created 280 confocal Z-stacks - the process that allows them to render the images in three dimensions - and was able to acquire quantitative data from 14 adult human colons. Additionally, they were able to visualize the ENS in children with Hirschsprung disease.

"We believe our new approach will help us understand bowel diseases in more detail and could lead to new approaches to therapy," Heuckeroth said.

The images generated from the study are now available on a public database.
-end-
This study was supported by the Suzi and Scott Lustgarten Endowment, the Irma and Norman Braman Endowment, Children's Hospital of Philadelphia Research Institute, National Institutes of Health NIH grants RO1DK087715, 5F30DK117546-02, and OT2OD02385, March of Dimes grant 6-FY15-235, The Burroughs Wellcome Fund Clinical Scientist Award in Translational Research, Abramson Cancer Center, the Human Pancreas Analysis Program, and Human Islet Research Network grant UC4DK112217.

Graham et al, "Robust, 3-Dimensional Visualization of Human Colon Enteric Nervous System Without Tissue Sectioning." Gastroenterology, online 27 Feb 2020.

About Children's Hospital of Philadelphia: Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. In addition, its unique family-centered care and public service programs have brought the 564-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu

Children's Hospital of Philadelphia

Related Cell Types Articles from Brightsurf:

AI methods of analyzing social networks find new cell types in tissue
In situ sequencing enables gene activity inside body tissues to be depicted in microscope images.

A new strategy of cell entry for some types of parvoviruses
Researchers at the Institut national de la recherche scientifique (INRS), in collaboration with American scientists, have uncovered a new parvovirus strategy for reaching the cell nucleus which is their site of replication.

Brain cell types identified that may push males to fight and have sex
Two groups of nerve cells may serve as ''on-off switches'' for male mating and aggression, suggests a new study in rodents.

Yale, Baylor study reveals new cell types in lethal lung disease
A research team from Yale and Baylor College of Medicine has completed the largest single-cell analysis to date of lungs affected by Idiopathic Pulmonary Fibrosis (IPF), revealing how cells change in response to the disease and identifying previously unknown cell types.

Novel software reveals molecular barcodes that distinguish different cell types
A new set of computational methods developed at Baylor College of Medicine allows researchers to identify cell-type specific methylation patterns -- molecular barcodes -- in complex cell mixtures.

Scientists devise new 'bar code' method to identify critical cell types in the brain
A discovery by researchers at Brown's Center for Translational Neuroscience could pave the way for future studies aimed at developing solutions to ALS and other vexing neuromuscular diseases.

AI successfully used to identify different types of brain injuries
Researchers have developed an AI algorithm that can detect and identify different types of brain injuries.

Eclectic rocks influence earthquake types
New Zealand's largest fault is a jumble of mixed-up rocks of all shapes, sizes, compositions and origins.

New knowledge on how different brain cell types contribute to our movements
Researchers at Karolinska Institutet have mapped how different nerve cells in the brain area striatum process information to plan and execute our movements at just the right time and with the right vigour.

Three types of cells help the brain tell day from night
Researchers at the Salk Institute report the discovery of three cell types in the eye that detect light and align the brain's circadian rhythm to our ambient light.

Read More: Cell Types News and Cell Types Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.