A study by scientists at Children's Hospital Los Angeles has shown that tissue-engineered colon derived from human cells is able to develop the many specialized nerves required for function, mimicking the neuronal population found in native colon.
These specialized neurons, localized in the gut, form the enteric nervous system, which regulates digestive tract motility, secretion, absorption and gastrointestinal blood flow. In addition, in a condition called Hirschsprung's disease or aganglionosis, where those neurons are not present, the team was able to replace them.
The study -- the first report on the enteric nervous system in human-derived tissue-engineered colon -- was published online ahead of print in the journal of Tissue Engineering, Part A on September 28.
In healthy intestines, food is moved along the digestive tract through peristalsis -- a series of wave-like contractions. Special nerve cells called ganglion cells are required for this movement, but there is also a rich mixture of other types of nerve cells. In children with Hirschsprung's disease, these cells are missing. Without them, the intestine becomes blocked and surgical removal of the affected segment of colon is required.
To help these and other children suffering from intestinal diseases that may require surgical removal of all or part of their intestine, the CHLA team -- led by principal investigator Tracy C. Grikscheit, MD, a pediatric surgeon and researcher at The Saban Research Institute of CHLA -- is developing tissue-engineered options for these children.
One objective of growing tissue-engineered organs is to generate new tissue from a patient's own cells. Grikscheit and her team first needed to determine what parts of the enteric nervous system were present in tissue-engineered colon when it is grown from normal human cells.
"The diversity of neuron types that grew within the human tissue-engineered colon was a revelation to our team, because previously we had only documented that some ganglia were present," said Grikscheit, who is also a tenured associate professor of Surgery at the Keck School of Medicine of the University of Southern California. "The next step was to determine if these neuronal elements could be supplied to tissue-engineered colon that was missing neurons - like in Hirschsprung's disease."
The scientists initially grew cells from patients with Hirschsprung's disease and from mice with a genetic mutation that causes aganglionosis. In both cases, the tissue-engineered colon derived from these cells did not have the all-important components of the intestinal nervous system. In a second set of experiments, again testing both mouse and human cells, the investigators added neurospheres, which are clusters of purified neural progenitor cells. The cells had been stained with green fluorescence, so the scientists could readily visualize where the nerve cells ended up in the tissue-engineered colon, as well as determine the source of the nerve cells.
"After growing the colon for four weeks, we saw that the green nerve cells had been incorporated into the colon engineered from human tissue derived from a patient lacking those elements and that the different nerve subtypes were present," said first author on the study, Minna Wieck, MD, an investigator and surgical resident at CHLA.
Additional contributors to the study include Wael N. El-Nachef, Xiaogang Hou, Ryan G. Spurrier, Kathleen A. Holoyda, Kathy A. Schall, Salvador Garcia Mojica, Malie K. Collins, and Andrew Trecartin of Children's Hospital Los Angeles; and Zhi Cheng, and Philip K. Frykman of Cedars-Sinai Medical Center, Los Angeles. Funding was provided in part by the California Institute of Regenerative Medicine (RN3 00946-1, RN3 06425, TG2-01168) and from the National Institute of Diabetes, Digestive and Kidney Diseases (K08DK090281).
Link to article: http://online.
About Children's Hospital Los Angeles
Children's Hospital Los Angeles has been named the best children's hospital in California and among the top 10 in the nation for clinical excellence with its selection to the prestigious U.S. News & World Report Honor Roll. Children's Hospital is home to The Saban Research Institute, one of the largest and most productive pediatric research facilities in the United States. Children's Hospital is also one of America's premier teaching hospitals through its affiliation since 1932 with the Keck School of Medicine of the University of Southern California. For more information, visit CHLA.org. Follow us on Twitter, Facebook, YouTube and LinkedIn, or visit our blog at http://researchlablog.
Ellin Kavanagh | EurekAlert!
Single-stranded DNA and RNA origami go live
15.12.2017 | Wyss Institute for Biologically Inspired Engineering at Harvard
New antbird species discovered in Peru by LSU ornithologists
15.12.2017 | Louisiana State University
DNA molecules that follow specific instructions could offer more precise molecular control of synthetic chemical systems, a discovery that opens the door for engineers to create molecular machines with new and complex behaviors.
Researchers have created chemical amplifiers and a chemical oscillator using a systematic method that has the potential to embed sophisticated circuit...
MPQ scientists achieve long storage times for photonic quantum bits which break the lower bound for direct teleportation in a global quantum network.
Concerning the development of quantum memories for the realization of global quantum networks, scientists of the Quantum Dynamics Division led by Professor...
Researchers have developed a water cloaking concept based on electromagnetic forces that could eliminate an object's wake, greatly reducing its drag while...
Tiny pores at a cell's entryway act as miniature bouncers, letting in some electrically charged atoms--ions--but blocking others. Operating as exquisitely sensitive filters, these "ion channels" play a critical role in biological functions such as muscle contraction and the firing of brain cells.
To rapidly transport the right ions through the cell membrane, the tiny channels rely on a complex interplay between the ions and surrounding molecules,...
The miniaturization of the current technology of storage media is hindered by fundamental limits of quantum mechanics. A new approach consists in using so-called spin-crossover molecules as the smallest possible storage unit. Similar to normal hard drives, these special molecules can save information via their magnetic state. A research team from Kiel University has now managed to successfully place a new class of spin-crossover molecules onto a surface and to improve the molecule’s storage capacity. The storage density of conventional hard drives could therefore theoretically be increased by more than one hundred fold. The study has been published in the scientific journal Nano Letters.
Over the past few years, the building blocks of storage media have gotten ever smaller. But further miniaturization of the current technology is hindered by...
11.12.2017 | Event News
08.12.2017 | Event News
07.12.2017 | Event News
15.12.2017 | Power and Electrical Engineering
15.12.2017 | Materials Sciences
15.12.2017 | Life Sciences