A research team recently grew a liver from stem cells. Laoise Fitzpatrick looks at the benefits of such a technique.
One of the main obstacles for pharmaceutical companies in drug development is testing the efficacy and safety of new drugs. In order to receive approval for a drug to be used in humans, it must undergo a lengthy process of testing in animals and humans, commonly known as clinical trials. Unfortunately for the companies, this is where many drugs fail: unforeseen side effects not apparent on the cellular level but only on the tissue, organ or system level render many promising drug candidates too dangerous for use. This means that every drug that does make it to market carries the cost of all the failed candidates before it. Now, however, researchers at the University of California San Diego have developed a technology that could dramatically reduce the time and cost incurred in developing new drugs.
The team of engineers led by Professor Shaochen Chen have successfully created a model liver, using a revolutionary 3D printing technique also developed by the team. The model is capable of accurately reproducing real liver function and physiology. According to professor Chen, a typical drug that passes clinical trial takes 12 years to develop and over $1.8 billion. His hope is that by testing drug candidates on this liver model, pharmaceutical companies can disregard those that display adverse effects and instead focus on a smaller group of more promising compounds.
The new model more accurately creates the complex cell structure and architecture of the liver, as well as its unique blood delivery system.
The liver is responsible for metabolising many drugs that enter the body, and so it is one of the organs most commonly affected by drug side effects. Attempts have been made to produce models of the liver before, but only simple two dimensional or spherical three dimensional models have been created. The new model more accurately creates the complex cell structure and architecture of the liver, as well as its unique blood delivery system. This will allow more accurate analysis of drug effects on the tissue. When tested against these other models, the new tissue showed improvements in key areas of interest such as albumin secretion and urea production.
The liver tissue is created using a unique “bio printing” technique developed by the team. Layers of hexagonal liver cells, each 900 microns wide, are produced from pluripotent stem cells. These are then supported by two types of proteins. As with other models, the resulting scaffold is then allowed to sit in a cell bath, for a period of 20 days. One major benefit over costly time consuming techniques in the past is the speed at which this can be performed. A 300 x 300 micron square sample can be made in a matter of seconds. The samples also performed for longer periods of time and produced larger amounts of key enzymes than other models.
While the main aim of the technology is to reduce the cost of developing new drugs, the models also have other possible uses. Due to the fact that pluripotent human stem cells are used, it is possible that liver tissue could be developed for individual patients to repair or replace areas of the liver that have been damaged by diseases such as cirrhosis. This might be some way in the future, but with fewer companies willing to spend billions on risky drug development, this technology shows promise in allowing more companies to enter the market and develop and test large numbers of unique treatments.