Functional tissue-engineered intestine grown from human cells

Los Angeles: Scientists have used human cells to grow tissue-engineered small intestine which mimics key aspects of a functioning human gut.

The tissue-engineered small intestine developed by researchers at Children's Hospital Los Angeles (CHLA) 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.

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.

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 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.

These cells are found within the engineered tissue in specific locations and in close proximity to other specialised 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 Tracy C Grikscheit, a principal investigator in The Saban Research Institute of CHLA.

"Demonstrating the functional capacity of this tissue-engineered intestine is a necessary milestone on our path toward one day helping patients with intestinal failure," she said.

The study is published in the American Journal of Physiology: GI & Liver.