Collaborative initiative led by Dr. D.C.F. Salvatori, Leiden University Medical Center
Replacement of the in vivo assay “teratoma” with a new in vitro bioinformatic assay for testing pluripotency of stem cells: development and validation.
Development and validation of in vitro assay testing pluripotency of stem cells.
Innovation, Human R&D
ZonMW – Grant ID 114021007
1 October 2013 to 30 September 2016
The startling discovery of 2007 that human somatic cells can be reprogrammed towards a pluripotent stem cell-like state (induced pluripotent stem cells, iPSC) has opened a new era for the understanding and treatment of human genetic diseases. Since then hundreds if not thousands of iPSC lines have been generated and the increase is expected to be exponential. The reason for this is that reprogramming is a relatively simple method on the one hand and that iPSC derivatives could be used in drug and toxicology testing as well as for customized cell replacement therapies in the future on the other hand. This project was set to replace the in vivo assay based on teratoma evaluation with a data driven in vitro test based on transcriptional profiling by microarray and next generation sequencing. Beside the method being animal-independent, the low cost and increasing accessibility of gene expression datasets makes transcriptional profiling an attractive and feasible alternative to determine pluripotency. GenomeScan provided genomic and transcriptomic tools to develop and validate the bioinformatic assay.
Differentiation-defective human induced pluripotent stem cells reveal strengths and limitations of the teratoma assay and in vitro pluripotency assays. Bouma MJ, et al. Stem cell reports. 2017 May 9;8(5):1340-53. doi: 10.1016/j.stemcr.2017.03.009.
This work was part of the ZonMW research programme with project number 114021007, which is (partly) funded by the Dutch Research Council (NWO).