A chemical tool for improved culture of human pluripotent stem cells
Silpa, L.; Schuessler, M.; Liu, G.; Olivecrona, M.; Groizard-Payeras, L.; Couper, E.; Bataille, C. J. R.; Stevenson, M.; Seymour, L. W.; Davies, S. G.; James, W. S.; Cowley, S. A.; Russell, A. J.
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The large-scale and cost-effective production of quality-controlled human pluripotent stem cells (hPSC) for use in cell therapy and drug discovery requires chemically-defined xenobiotic-free culture systems that enable easy and homogeneous expansion of pluripotent cells. Through phenotypic screening, we have identified a small molecule, OXS8360 (an optimized derivative of (-)-Indolactam V ((-)-ILV)), that stably disrupts hPSC cell-cell contacts. Proliferation of hPSC in OXS8360 is normal, as are pluripotency signatures, directed differentiation to hallmark lineages and karyotype over extended passaging. In 3D culture, OXS8360-treated hPSC form smaller, more uniform aggregates, that are easier to dissociate, greatly facilitating expansion. The mode of action of OXS8360 involves disruption of the localisation of the cell-cell adhesion molecule E-cadherin, via activation of unconventional Protein Kinase C isoforms. OXS8360 media supplementation is therefore able to yield more uniform, disaggregated 2D and 3D hPSC cultures, providing the hPSC field with an affordable tool to improve hPSC quality and scalability.
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