Researchers from the MRC Centre for Regenerative Medicine at the University of Edinburgh managed to transform embryonic stem cells into 3D human liver tissue which later they implanted into mice with liver pathology. The results turned out to be fairly promising.
Besides being potentially beneficial for developing human liver tissue implants for transplantation this technology may also help to reduce the number of animals used in the labs for testing new drugs or investigating human liver diseases.
The results of the study were published in the journal Archives of Toxicology. The researchers used human embryonic stem cells and induced pluripotent stem cells (mature cells which were made to turn back into stem cells) and gently stimulated them to develop the features of hepatocytes. The main outstanding fact is that they have been growing these cells for over a year.
Professor David Hay from the MRC Centre for Regenerative Medicine at the University of Edinburgh, who was in the head of this research, commented: “This is the first time anyone has kept stem cell-derived liver tissue alive for more than a year in the lab. Keeping the cells alive and stable as liver cells for a long time is a very difficult step, but crucial if we hope to use this technology in people.”
After growing these cells scientists from the Centre for Regenerative Medicine together with materials chemists and engineers were trying to find appropriate polymers already approved for use in humans so that to make 3D scaffolds and put liver cells into them They have eventually identified the most suitable material which was biodegradable polyester, polycaprolactone. So researches took hepatocytes, put them into the scaffolds and implanted under mice skin. They have noted that new blood vessels successfully grew on the scaffolds and human liver proteins were detected in their blood. Taken together, these data meant that liver tissue had successfully integrated with the blood circulatory system.
Scaffolds loaded with liver tissue were also tested on mice with tyrosinaemia. Tyrosinemia is a rare autosomal recessive genetic metabolic disorder characterized by lack of the enzyme fumarylacetoacetate hydrolase (FAH), which is needed for the final break down of the amino acid tyrosine. Failure to properly break down tyrosine leads to abnormal accumulation of tyrosine and its metabolites in the liver, potentially resulting in severe liver disease. Scientists have found that mice with hepatocytes implants lost less weight, had less concentration of toxins in the blood, and had fewer signs of liver damage.
Dr Rob Buckle, Chief Science Officer at the MRC, stated: “This research brings us a step closer to harnessing the potential of stem cell ‘reprogramming’ technologies to provide renewable supplies of liver tissue products for transplantation.”