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The future of drug development: a stem cell-derived liver

 

Yan-Ru Lou, Faculty of Pharmacy, University of Helsinki

PhD Yan-Ru Lou develops a stem cell-derived 3D liver for drug development purposes.

 

29 September 2015

A 3D liver derived from stem cells could speed up the drug discovery process and eventually pave the way to personalised drugs.

University researcher, PhD Yan-Ru Lou has been working with stem cells for nearly a decade. She began her work in Tampere, continued it in Singapore, and since 2009 has been working in the Faculty of Pharmacy. Now she has taken on a real challenge: building a functioning liver for drug development. Even if 3D liver will be created from stem cells in vitro, it will work like a real one.

Life-like liver functions are in great need in drug development.

"Liver damages are the most common type of drug-related injuries , accounting for as many as one in three drug-related injuries. And because drug development is so slow and expensive process, any means to speed it up are welcome. Predictive cell models, such as the 3D liver, promise to help us to identify liver-damaging drugs early and to eliminate them from the drug development chain," notes Yan-Ru Lou.

Predictive cell models are also welcome because they help to reduce the use of animals in drug testing. Using animals is not only a question of ethics, but species differences make animals less reliable subjects in drug testing. A drug that works in one animal species may not work at all or could even prove harmful in humans.

 

Stem cells and matrix

Two types of stem cells can be used when building a liver from stem cells: human pluripotent stem cells and liver-specific stem cells.

Pluripotent stem cells are not only easier to obtain from the same donor, because they can be generated from skin or blood cells, but they also proliferate well. The problem with pluripotent stem cells is that they can be differentiated into any cell type, so they need many steps and careful coaxing to become liver cells, or hepatocytes.

" Tissue-specific stem cells are easier in that they are already half way to becoming hepatocytes. On the other hand, they do not proliferate as eagerly as the pluripotent stem cells do. And obtaining them requires more invasive procedures, because they must be taken from the liver," says Yan-Ru Lou.

Just a suitable biochemical environment is not enough for stem cells to mature into functional hepatocytes; to work properly, they need a three-dimensional (3D) matrix in which to grow. Yan-Ru Lou has two options: hydrogels or a decellularised matrix.

 

Aiming for personalised medicine

When researchers have succeeded in clearing all the obstacles from the path towards a stem cell-derived liver, the next goal is to use the 3D liver to create personalised medicines.

"People’s responses to drugs differ greatly. If you grow a 3D liver from a patient’s own stem cells, you can test how the patient responses to the drug without harming the patient. If everything goes smoothly, it takes about two weeks for liver stem cells to mature and to begin working properly," estimates Yan-Ru Lou, who has secured special risk-taking funding for her project from the Academy of Finland.

In addition to Yan-Ru Lou’s project, two other projects in the Faculty of Pharmacy also obtained risk-taking funding. These projects, by Leena Kontturi and Tapani Viitala, will be presented later on the Faculty's web pages.