Researchers at Edinburgh University have developed a novel synthetic polymer matrix that overcomes current issues of stability and viability. A defined supporting basement matrix is provided that significantly improves the morphology, lifespan and function of hepatocytes derived from human embryonic stem cells (hESCs).
Scalable and reproducible generation of hepatocyte endoderm (HE) is of interest for cell-based therapy, drug and toxicology testing and for use in bio-artificial liver devices. Use of hESC-derived HE has the potential to provide genetically diverse, cheap and stable hepatocytes. However, current methods produce phenotypically unstable cells.
The polymer identified at Edinburgh overcomes these problems. When HE derived by this method is compared to HE raised on Matrigel, cells show improved morphology, changes in cell signalling consistent with attachment, metabolically active cells and absence of apoptosis.
Additionally, enhancement of expression of proteins involved in hepatocyte biology is observed, with a more than 2-fold enhanced expression of Fibrinogen, transthyretin and CYP3A4 and a 6-fold increase of CYP1A2.
Production of the matrix is cost effective, straightforward and scalable, and the matrix is adaptable for clinical use and can be easily manufactured to GMP conditions. In addition, the matrix is flexible, as it has been shown to be an effective surface for maintaining hepatocytes generated from different cellular sources. The cells are proven to be predictive of toxicology in a bio-artificial liver device, and derived hepatocyte like cells show improved morphology and long-term stability.
Data are available demonstrating that hepatocyte-like cells grown on this polymer show improved morphology, long-term stability and enhancement of expression of marker linked to hepatocyte biology.
A patent application (Reference PCT/GB2010/000523), entitled, “Use of polymer for cell growth,” has been filed with a priority date of 20th March 2009.
Edinburgh University is seeking a commercial partner to manufacture and sell a new cell culture reagent. The research team are also available to undertake collaborative research. Samples of the polymer can be made available to test.
For more information, visit the project’s website at: http://www.university-technology.com/details/novel-polymers-for-improved-hepatocytes