Our group recently reported a model system which allows

Our group recently reported a model system, which allows to effectively screen whole miRNA libraries for miRNA candidates modulating reprogramming efficacy (Pfaff et al., 2011). Utilizing this model, we previously have identified a miRNA family consisting of miR-130b, miR-301b, and miR-721 strongly enhancing iPSC generation. In our current work, we have analyzed those miRNAs that abrogate iPSC generation and investigated whether the inhibition of those miRNAs can in turn support iPSC generation.
Material and methods
Results and discussion
Conclusion
Disclosure of potential conflicts of interest
Author contributions
Acknowledgement We thank Doreen Lüttge for an excellent technical assistance and Reto Eggenschwiler for support of the miR-199a-5p modulation experiments. Furthermore, we thank Ursula Rinas (Leibniz University Hannover) for providing leukemia inhibitory factor (LIF). Parts of the study were funded by the German Research Foundation (EXC 62/3, REBIRTH Excellence Cluster), the Fondation Leducq (Project MIRVAD), the German Federal Ministry of Education and Research (IFB-Tx, BMBF 01EO1302; 01GM0854; and 01GP1007c) and the Hochschulinterne Leistungsförderung (HiLF) program of MHH (NP).
Introduction Since their introduction in 2007 (Takahashi et al., 2007) hiPSC have been rapidly and broadly incorporated into research to understand their potential for disease. This has substantiated interest to incorporate this resource into drug discovery pipelines, prospective patient stratification, recruitment for clinical trials and post-clinical drug assessment of safety issues following rare event reporting. However, the apigenin of these applications depends on facilitated and unfettered access to a standardised and well characterised hiPSC resource to help avoid dissemination of unauthenticated or substandard cell lines to the research community. Rising demand by academia and industry has instigated a number of large scale public and privately funded disease and/or population oriented hiPSC banking initiatives in the US, Japan and UK (McKernan and Watt, 2013). These will foreseeably improve the consistency with which new cell lines will be developed but not necessarily the standardised and scalable distribution of pre-established or new lines to the wider hiPSC research community. At present in Europe, a human pluripotent stem cell registry (www.hPSCreg) offers the research community, legislators, regulators and the general public a measured overview of the current status of human pluripotent stem cell research though the provision of information on established cell lines derived from embryos or induced from adult cell sources. At time of writing over 452 hiPSC lines are on the registry, sponsored by EU, nation specific and charitable funding sources. However, this resource does not facilitate standardise access to these resources which still require user interface with institutional representatives in possession of any given cell line. Recognising a need for a harmonised framework of best practice, the Innovative Medicines Initiative Joint Undertaking (IMI JU), a pan-European public private partnership between the European Commission (EC) and European Federation of Pharmaceutical Industries and Associations (EFPIA; www.efpia.eu), issued a call for proposals which in January 2014 culminated in the launch of the European Induced Pluripotent Stem Cell Bank (EBiSC). EBiSC\'s mission has been to: i) identify key cohorts of patients useful for research purposes within the wider scientific community, ii) create a large single European hiPSC repository through the integration of existing infrastructure, such as for example hPSCreg, and iii) generate a centre of scientific excellence for standardisation and optimisation of cryopreservation, retrieval and differentiation methods for hiPSC lines. Here we report on the experience of the first stage of this initiative, a fast track “Hot Start” process whose goal was to rapidly establish operational capacity and a distributable foundational collection of established hiPSC lines.