Tag Archives: Jeffrey Ryan Hill

Engineering a small intestine

Researchers at the Children’s Hospital Los Angeles (CHLA) have successfully engineered small intestines that appear to be functional when transplanted into mice according to a Jan. 8, 2015 news item on ScienceDaily,

A new study by researchers at Children’s Hospital Los Angeles has shown that tissue-engineered small intestine grown from human cells replicates key aspects of a functioning human intestine. The tissue-engineered small intestine they developed contains important elements of the mucosal lining and support structures, including the ability to absorb sugars, and even tiny or ultra-structural components like cellular connections.

A Jan. 8, 2015 Children’s Hospital Los Angeles news release (also on EurekAlert), which originated the news item, describes the problems the researchers were addressing,

Tissue-engineered small intestine (TESI) grows from stem cells contained in the intestine and offers a promising treatment for short bowel syndrome (SBS), a major cause of intestinal failure, particularly in premature babies and newborns with congenital intestinal anomalies.  TESI may one day offer a therapeutic alternative to the current standard treatment, which is intestinal transplantation, and could potentially solve its largest challenges – donor shortage and the need for lifelong immunosuppression.

Grikscheit [Tracy C. Grikscheit, MD, a principal investigator in The Saban Research Institute of CHLA and its Developmental Biology and Regenerative Medicine program]  aims to help her most vulnerable young patients, including babies who are born prematurely and develop a devastating disease called necrotizing enterocolitis (NEC), where life-threatening intestinal damage requires removal of large portions of the small intestine. Without enough intestinal length, the babies are dependent on intravenous feeding, which is costly and may cause liver damage.  NEC and other contributors to intestinal failure occur in 24.5 out of 100,000 live births, and the incidence of SBS is increasing.  Nearly a third of patients die within five years.

The news release goes on to describe precursor work from 2011 before describing the latest research,

CHLA scientists had previously shown that TESI could be generated from human small intestine donor tissue implanted into immunocompromised mice. However, in those initial studies – published in July 2011 in the biomedical journal Tissue Engineering, Part A – only basic components of the intestine were identified. For clinical relevance, it remained necessary to more fully investigate intact components of function such as the ability to form a healthy barrier while still absorbing nutrition or specific mechanisms of electrolyte exchange.

The new study determined that mouse TESI is highly similar to the TESI derived from human cells, and that both contain important building blocks such as the stem and progenitor cells that will continue to regenerate the intestine as a living tissue replacement. And these cells are found within the engineered tissue in specific locations and in close proximity to other specialized cells that are known to be necessary in healthy human intestine for a fully functioning organ.

“We have shown that we can grow tissue-engineered small intestine that is more complex than other stem cell or progenitor cell models that are currently used to study intestinal regeneration and disease, and proven it to be fully functional as it develops from human cells,” said Grikscheit. “Demonstrating the functional capacity of this tissue-engineered intestine is a necessary milestone on our path toward one day helping patients with intestinal failure.”

If I read this rightly, the researchers engineered more complex intestinal tissues, than those in the 2011 study, in two separate processes where they grew mouse and human small intestinal tissue and successfully implanted both types of tissue into mice. The results showed that these more complex tissue-engineered small intestines (TESIs), human or mouse, resembled each other functionally within the mice tested.

Here’s a link to and a citation for the paper,

Human and Mouse Tissue-Engineered Small Intestine Both Demonstrate Digestive And Absorptive Function by Christa Nicole Grant, Garcia Mojica Salvador, Frederic G Sala, Jeffrey Ryan Hill, Daniel E Levin, Allison L Speer, Erik R Barthel, Hiroyuki Shimada, Nicholas C. Zachos, and Tracy C. Grikscheit. American Journal of Physiology – Gastrointestinal and Liver Physiology Published 8 January 2015Vol. no. , DOI: 10.1152/ajpgi.00111.2014

This paper is behind a paywall.