sebasgr

• Siller, Richard; Naumovska, Elena; Mathapati, Santosh Sadashiv; Lycke, Max; Greenhough, Sebastian & Sullivan, Gareth (2016). Development of a rapid screen for the endodermal differentiation potential of human pluripotent stem cell lines. Scientific Reports. 6. doi: 10.1038/srep37178. Fulltekst i vitenarkiv Vis sammendrag

  A challenge facing the human pluripotent stem cell (hPSC) field is the variability observed in differentiation potential of hPSCs. Variability can lead to time consuming and costly optimisation to yield the cell type of interest. This is especially relevant for the differentiation of hPSCs towards the endodermal lineages. Endodermal cells have the potential to yield promising new knowledge and therapies for diseases affecting multiple organ systems, including lung, thymus, intestine, pancreas and liver, as well as applications in regenerative medicine and toxicology. Providing a means to rapidly, cheaply and efficiently assess the differentiation potential of multiple hPSCs is of great interest. To this end, we have developed a rapid small molecule based screen to assess the endodermal potential (EP) of hPSCs, based solely on definitive endoderm (DE) morphology. This drastically reduces the cost and time to identify lines suitable for use in deriving endodermal lineages. We demonstrate the efficacy of this screen using 10 different hPSCs, including 4 human embryonic stem cell lines (hESCs) and 6 human induced pluripotent stem cell lines (hiPSCs). The screen clearly revealed lines amenable to endodermal differentiation, and only lines that passed our morphological assessment were capable of further differentiation to hepatocyte like cells (HLCs).

• Siller, Richard; Greenhough, Sebastian; Naumovska, Elena & Sullivan, Gareth (2015). Small-molecule-driven hepatocyte differentiation of human pluripotent stem cells. Stem Cell Reports. ISSN 2213-6711. 4(5), s. 939–952. doi: 10.1016/j.stemcr.2015.04.001. Fulltekst i vitenarkiv Vis sammendrag

  The differentiation of pluripotent stem cells to hepatocytes is well established, yet current methods suffer from several drawbacks. These include a lack of definition and reproducibility, which in part stems from continued reliance on recombinant growth factors. This has remained a stumbling block for the translation of the technology into industry and the clinic for reasons associated with cost and quality. We have devised a growth-factor-free protocol that relies on small molecules to differentiate human pluripotent stem cells toward a hepatic phenotype. The procedure can efficiently direct both human embryonic stem cells and induced pluripotent stem cells to hepatocyte-like cells. The final population of cells demonstrates marker expression at the transcriptional and protein levels, as well as key hepatic functions such as serum protein production, glycogen storage, and cytochrome P450 activity.

• Siller, Richard; Greenhough, Sebastian; Park, IH & Sullivan, Gareth (2013). Modelling Human Disease with Pluripotent Stem Cells. Current Gene Therapy. ISSN 1566-5232. 13(2), s. 99–110. doi: 10.2174/1566523211313020004. Fulltekst i vitenarkiv

Se alle arbeider i NVA