The European Bank of Induced Pluripotent Stem Cells: Five Years of Progress – Technology Networks

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Since Yamanakas demonstration in 2006 that adult cells can be reprogrammed to an embryonic stem cell-like state using a specific cocktail of transcription factors, interest in the development and use of induced pluripotent stem cells (iPSC) has flourished. The potential for these cells to be used as models for drug discovery and disease research, as well as therapeutics, has resulted in more and more researchers seeking access to iPSCs.

In a bid to meet this increasing demand for quality-controlled, disease-relevant, research-grade iPSC lines, a project began in 2014 to set up the first European Bank of induced Pluripotent Stem Cells (EBiSC). Five years on and the project entered its second phase, with the aim of becoming a self-sustainable central iPSC hub by 2022.

Here,Technology Networks speaks to Rachel Steeg, Project Manager, Fraunhofer UK Research Ltd and a coordinator of EBiSC activities, to discuss phase two of the project and discover some of the benefits it is bringing to the scientific community. Anna MacDonald (AM): Can you give us an overview of EBiSC? Rachel Steeg (RS): EBiSC is a centralised, non-profit, iPSC repository with central facilities in Germany and the UK which safeguards iPSC lines derived both from within EBiSC and from external research centres. Once iPSC lines are shared with EBiSC, we perform expansion, banking and quality control at one of our central facilities according to user demand. Data are shared to users via the EBiSC catalogue (https://cells.ebisc.org/) with genomic datasets available through application to the EBiSC Data Access Committee (DAC). EBiSC lines can be ordered directly from the European Collection of Authenticated Cell Cultures (ECACC) and after completion of a single Access and Use Agreement and a Cell Line Information Pack for each line, ECACC can ship worldwide either on dry ice or using a dry shipper. Every iPSC line is securely stored at our Mirror Facility at the Fraunhofer Institute for Biomedical Engineering (IBMT) in Germany where an ASKION database, cryo-workbench and hermetic storage tanks track vials using barcodes, ensuring an uninterrupted cold-chain. A second project phase, currently in progress, is streamlining and optimising these core processes as well as developing new iPSC products and services.

AM: What was the motivation behind the project, and how did it get started? RS: Its now widely recognised that iPSC lines hold great promise for changing the way we investigate disease pathologies and discover new therapeutics, but issues around poor traceability, limited access and poor quality, are seen as limiting factors in really progressing with this avenue of research. EBiSC was initially launched in 2014 through a public-private partnership with IMI (Innovative Medicines Initiative) and EFPIA (European Federation of Pharmaceutical Industries and Associations) with a core goal of tackling these issues aiming to making high quality and disease relevant iPSC lines with associated datasets, adult cells can be reprogrammed to an embryonic stem cell-like state. Hence, the focus from the outset was to build an infrastructure that would allow EBiSC to accept iPSC lines from multiple sources and standardise them for downstream use. Sharing the data associated with these lines has been really key in this process, including sharing details of the consent, donor disease information and iPSC characterisation data in an anonymised way via hPSCreg and allowing access to sensitive datasets such as Whole Genome Sequencing through the EBiSC DAC. Finally, EBiSC eased the often lengthy process for completing transfer agreements by implementing a procedure which allows users to access lines from multiple sources under one single agreement.

AM: Why is there an increasing demand for iPSC lines? RS: As protocols detailing the maintenance and downstream use of iPSCs develop, their use in drug discovery, particularly using mature differentiated cell populations, has become easier and easier to implement. Critically, as high-quality iPSC lines are now available through repositories such as EBiSC, researchers can focus on their key research question at hand, rather than investing precious resources on accessing appropriate, fully consented patient biosamples and generating new iPSC lines from scratch. Theres also an increasing awareness that use of current animal and simplistic cell models such as transgenic primary lines is likely contributing to the high failure rates in developing novel, effective and safe therapies and a new approach is needed including incorporating iPSCs as a disease relevant human model during pre-clinical investigations.

AM: The second phase of the project was launched March 2019. What can we expect to see during this phase of development? RS: The current second project stage, again supported by IMI2, will ensure that EBiSC is legally, ethically and financially sustainable long-term by widening the products and services on offer. As well as continuing to collect and provide iPSC lines, EBiSC will also provide disease relevant differentiated cell populations such as cardiomyocytes and neurons, including sharing them in an assay ready-to-use format. As mentioned, EBiSC already has a robust infrastructure for generating, genetically modifying, banking, qualifying and distributing iPSC lines so we are now opening up this infrastructure for external use researchers can just get in touch with EBiSC and ask for help with any of these activities as a non-profit, fee-for-service activity, with revenue feeding back into the bank.

AM: What difference can having access to iPSCs from the bank make to scientists and their research? RS: For many of the disease associations represented by EBiSC, multiple lines are available from the same disease background, helping researchers achieve statistical significance in their research. By accessing iPSC lines from EBiSC, its also not just the iPSC lines themselves which can make the difference. In addition to the datasets mentioned previously and the provision of high-quality iPSC cohorts, iPSC banking, QC protocols and best practice training resources are available through the EBiSC website. EBiSC also ensures fully anonymised traceability of each line, meaning that any consent, third party or licencing restrictions which may apply, are clearly flagged to users prior to purchase.

AM: In addition to the cells, what support can EBiSC offer to researchers? RS: Protocols for how to thaw, expand and cryopreserve iPSC lines are available via the website, as are recommendations as to how users should monitor their cultures both visually and through performing routine QC. Training videos advise users on best practice and Certificates of Analysis give cell line specific recommendations for thawing and passaging. Critically, EBiSC2 now offers iPSC services, including cell line generation, gene-editing, expansion and banking (including generation of banks of >100 vials) and qualifying iPSC lines using the established EBiSC Quality Control regime.

AM: Is it possible to deposit cells in the collection? What are the main benefits of doing this? RS: Yes! Any researcher worldwide can deposit iPSC lines into EBiSC, they just need to reach out to EBiSC either through the website or by emailing us at EBiSC@eurtd.com. Theres a whole host of benefits to deposition, including always having a secure multi-site back-up of your cell line stocks, access to EBiSC generated Quality Control and characterisation data and not having to find capacity for banking and agreeing MTAs if someone wants to access your line(s). One of the main benefits highlighted by current depositors is that deposition ensures sustainability of resources after project completion, both for themselves and to satisfy funding requirements. Best of all, deposition just grants EBiSC a non-exclusive licence to share the line(s), so researchers are still free to use and share their iPSC lines as they prefer, retaining their ownership and intellectual property of the lines.

Rachel Steeg was speaking to Anna MacDonald, Science Writer, Technology Networks.

Acknowledgements:

EBiSC2 is supported as a multinational public-private Innovative Medicines Initiative in its second phase (IMI2, 2014-2020, http://www.imi.europa.eu) under grant agreement No 821362. The IMI2 Joint Undertaking receives support from the European Unions Horizon 2020 research and innovation programme and EFPIA.

The content presented in the present publication reflect only the author's view and the Innovative Medicines Initiative 2 Joint Undertaking is not responsible for any use that may be made of the information it contains.

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The European Bank of Induced Pluripotent Stem Cells: Five Years of Progress - Technology Networks