Stem cell scientists have made a key find that aids the quest to produce therapies for patients with liver damage. They have developed a new technique for growing liver cells from stem cells that is cost-effective and could be adapted for mass production of clinical grade cells.
The process involves growing cells on defined materials – without the need for animal products – which scientists say makes therapies safer for use in people.
Liver cells have already been used as therapies for patients with liver damage with some success. At the moment, donor organs are the only source of cells. Growing liver cells from stem cells could offer a limitless supply for patient therapies, but the conditions currently used to grow these cells are not amenable to mass production. Existing methods also rely on the use of animal products derived from tumours, which means that the cells produced in this way cannot be given to patients.
Scientists from the Medical Research Council Centre for Regenerative Medicine at the University of Edinburgh have developed a new technique for growing the cells that uses synthetic material instead of animal products. The process involves synthetic versions of naturally occurring molecules called laminins. Laminins are part of the supportive scaffold that surrounds cells and shapes the complex structure of a tissue.
The team found that growing stem cells on laminins turned them into organised liver cells more efficiently than previous methods. The resulting cells were more similar to liver cells that have been freshly isolated from a donor organ. They showed similar patterns of gene expression and also arranged themselves to form complex structures that are found in liver tissue.
Researchers say this marks a significant step towards the large scale production of high quality liver cells for use as patient therapies. The study is published in the journal Stem Cell Reports. It was funded by the UK Regenerative Medicine Platform, the European Union Seventh Framework Programme (FP7) and the German Federal Ministry of Education and Research (BMBF).
Dr Dave Hay, of the University’s MRC Centre for Regenerative Medicine, said:
The development of a defined process to deliver better quality liver cells from clinical grade stem cells is a significant advance. The next step will be to assess their suitability for human use in the appropriate pre-clinical models.
Dr Rob Buckle, Director of Science Programmes at the MRC, said:
The ability to create therapeutic stem cells in a cost-effective and safe way is at the heart of the UK Regenerative Medicine Platform. It provides the tools and brings together the expertise needed to develop new therapeutic approaches, encouraging fundamental research to be targeted towards specific disease challenges. This project is an excellent example where that is being done and the value of the Platform which has been established.
Cameron K, Tan R, Schmidt-Heck W, Campos G, Lyall MJ, Wang Y, Lucendo-Villarin B, Szkolnicka D, Bates N, Kimber SJ, Hengstler JG , Godoy P, Forbes SJ, Hay DC. 2015. Recombinant laminins drive the differentiation and self-organisation of hESC-derived hepatocytes. Stem Cell Reports.
Summary of the publication
Stem cell derived somatic cells represent an unlimited resource for basic and translational science. While promising, there are significant hurdles that must be overcome. Our focus is on the generation of the major cell type of the human liver, the hepatocyte. Current protocols produce variable populations of hepatocytes, which is the product of using undefined components in the differentiation process. This serves as a significant barrier to scale up and application. To tackle this issue, we have designed a defined differentiation process using recombinant laminin substrates to provide instruction. We demonstrate efficient hepatocyte specification, cell organisation, and significant improvements in cell function and phenotype. This is driven in part by the suppression of unfavourable gene regulatory networks which control cell proliferation and migration, pluripotent stem cell self-renewal, and fibroblast and colon specification. We believe that this represents a significant advance, moving stem cell based hepatocytes closer towards biomedical application.