Main Category: Transplants / Organ Donations
Also Included In: Stem Cell Research
Article Date: 14 Oct 2013 – 1:00 PDT
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.
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The team was also able to show that these human foregut stem cells do not form tumours, which means that they can be safely injected for therapeutic purposes, without having adverse side effects.
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Stem cell breakthrough could set up future transplant therapies
The result was a much purer, self-renewing population of human foregut stem cells (hFSCs). The cells generated are true stem cells because they are able to self renew and can differentiate towards any part of the foregut. Because they are also still at the stage where they self-renew, they could be grown in large enough numbers to be used in clinical therapies.
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.
To address these limitations, the research team carried out a detailed study of the conditions in which stem cells differentiate specifically into the human foregut – the section of the digestive system extending from the mouth to the duodenum, and including the liver and pancreas.
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.
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.
By manipulating the signal pathways of the cells, and varying the environment in which the cells were developed and the substrate on which they were grown, they were able to isolate the precise culture needed for the differentiation of cells associated with the foregut itself. When heavily contaminated stem cell populations were developed under these conditions, the contaminating, non-endodermal cells eventually stopped proliferating and gradually disappeared. The universal nature of this culture system takes a step towards a universal system that could be used to treat any patient requiring cells for transplantation purposes.
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.
Unfortunately, the approach is far from perfect. In particular, it is difficult to produce a pure population of the required progenitors, and “contaminating” cells of the wrong type are typically found within the cell culture. This makes it difficult to identify the target cells for further differentiation in the lab and can complicate the application of these cells in transplant therapies. In some cases, hPSCs also produce such a large number of contaminating cells that the precursor population becomes unusable.
“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.”
The team is now building on the research by studying the fundamental mechanisms which control the differentiation of hFSCs specifically as liver cells or pancreatic cells, to further improve the production of these cell types for regenerative medicine.
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