Stem cell breakthrough could set up future transplant therapies

23 hours ago Foregut stem cells (green) differentiated into pancreatic cells expressing insulin. The development method pioneered by Cambridge researchers enables the production of an uncontaminated population of foregut cells, which could then be further differentiated as pancreatic cells for therapeutic use. Credit: Nicholas Hannan

A new method for creating stem cells for the human liver and pancreas, which could enable both cell types to be grown in sufficient quantities for clinical use, has been developed by scientists.

Using the technique, researchers have for the first time been able to grow a pure, self-renewing population of stem cells specific to the human foregut, the upper section of the human digestive system.

These so-called "Foregut stem cells" could then be developed further to produce liver or pancreatic cells. The method significantly improves on existing techniques for cultivating this type of stem cell, and raises the possibility that, with further work, they could be grown in large numbers in bioreactors. That would make it possible to use them for regenerative therapies, repairing damaged organs or tissues in the body, and treating conditions such as type I diabetes or liver disease.

"We have developed a cell culture system which allows us to specifically isolate foregut stem cells in the lab," Dr Nicholas Hannan, from the University of Cambridge Wellcome Trust MRC Stem Cell Institute, Department of Surgery, explained. Hannan led the study, which was carried out in the lab of Dr Ludovic Vallier.

"These cells have huge implications for regenerative medicine, because they are the precursors to the thyroid upper airways, lungs, liver, pancreas, stomach and biliary systems. We now have a system where we may be able to create all these cell types from the same starting population."

As reported in the journal Stem Cell Reports, the method also means that researchers will be able to analyse the embryonic development of foregut cells in greater depth. "We now have a platform from which we can study the early patterning events that occur during human development to produce the intestines, liver, lungs and pancreas," Hannan added.

The approach marks a breakthrough because it overcomes some of the problems which currently limit scientists' abilities to grow cells associated with the liver, pancreas, and other parts of the foregut in sufficiently large numbers for clinical use.

Stem cell growth starts with human pluripotent stem cells (hPSCs). These are non-specialised biological cells with the potential to transform - or "differentiate" - into any of the three primary layers of cells from which all tissues and organs develop. Because these cells also self-renew, creating copies of themselves, they offer the potential to provide an infinite source of clinically usable cells for regenerative medicine.

Achieving this, however, relies on scientists developing effective methods through which they can influence the differentiation of hPSCs. To grow pancreatic or liver cells, hPSCs are differentiated into the endoderm - the primary tissue layer associated with the digestive and respiratory systems. This provides a base population of progenitors which researchers can then try to develop as more specialised cells.

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Stem cell breakthrough could set up future transplant therapies