Laminins Key to Production-Scale Stem Cell Development

Growing differentiated cells from stem cells may now be a bit easier than before, thanks to the findings from a new study on the production of liver cells. The study, backed by the Centre for Regenerative Medicine and published in Stem Cell Reports, finds that laminins may be a crucial element for the successful clinical-scale production and culture of stem cell therapies. The UK Regenerative Medicine Platform, the European Union Seventh Framework Programme, and the German Federal Ministry of Education and Research funded the research.

Laminins, which are extracellular proteins that are thought to be influential in cell differentiation, migration, differentiation repair, and adhesion, could provide an anchoring substrate to help difficult-to-culture stem cells thrive. Although researchers have explored the function of laminins in the past, these were typically mouse sarcoma-derived models; there are few reproducible animal-free options that are not associated with significant batch-to-batch variations. According to a press release from the Centre for Regenerative Medicine, existing methods rely on the use of animal tumor-sourced products, which could potentially prove immunogenic to humans.

Researchers showed that certain laminins-used as substrates for human embryonic stem cell-derived (hESC-derived) differentiation-could prompt favorable "hepatocyte specification and significant improvements in cell function and phenotype" compared with the substrate Matrigel, which is the most commonly used extracellular matrix (ECM). Additionally, stem cell-derived hepatocytes grown on laminin substrates "formed organized structures, and their gene regulatory networks were closer to that of freshly isolated human hepatocytes." In summary, hepatocyte gene expression (phenotype) was better for cells grown on laminin than for those on Matrigel. Importantly, laminin better controlled expression of undifferentiated genes-or the suppression of genes that are not specific to the liver-in the cells of interest. The researchers concluded that the presence of laminins facilitated the large-scale production of human hepatocytes from hESCs and drastically improved cell culture conditions.

"The development of a defined process to deliver better quality liver cells from clinical-grade stem cells is a significant advance," noted Dave Hay, group leader of the Pluripotent Stem Cell Hepatocyte Development team at the University of Edinburgh's Medical Research Council Centre for Regenerative Medicine, in a press release. "The next step will be to assess their suitability for human use in the appropriate preclinical models."

Sources: Stem Cell Reports, Medical Research Council