UK Stem Cell Bank Application for Phase V Funding 2017-2020

Regenerative medicine is a new and exciting field in clinical science with great promise for the treatment of traumatic injury and a range of currently incurable serious human diseases. Recent years have seen dramatic progress in this area, generating a diverse and complex range of potential therapies for which there is strong pressure to progress to clinic without delay. Such rapid development means that there is an ever shortening 'proving' period between translation and application of stem-cell based medicines in which to gain key understanding of the crucial issues for product safety and efficacy. Regenerative medicine development is still largely done by SMEs and academic research groups, often with limited resources and lack of internal regulatory science support. Close interaction within the regenerative medicine community to utilise experience from expert groups, is therefore crucial to long term success for this industry in the UK. The UK Stem Cell Bank (UKSCB) has established a long and effective track record in supplying quality assured and ethically sourced starting cells for advanced therapies and providing scientific advice and training to industry, academia and policy makers. As clinical trials in cell therapy roll-out internationally, such support activities will be vital in avoiding wasted time and resource on poor quality starting materials and to assist the smooth and safe progression of new cell therapy products to widespread use and acceptability.
The ultimate intent of the UKSCB is to sustain crucial ethical and scientific rigour in the use of human stem cell lines, whilst utilising its expertise and knowledge to enhance UK translational research to facilitate the safe and effective delivery of advanced cell therapies.
The primary objectives of the UKSCB are:
1) To curate samples of each ethically approved human embryonic stem cell (hESC) line and assure suitability of appropriately derived lines for clinical use under UK and EU regulation.
2) To enhance the efficiency, capacity and utility of the UKSCB clinical grade (EUTCD-Grade) cell line resource by further streamlining of banking procedures. This will include closer coordination with expert UK and international research groups to expand data sets to promote the value of UKSCB-held lines for human application.
3) To deliver a translational research programme supported by NIBSC core funding focused on: 1) developing enhanced banking processes and 2) crucial standardisation and safety issues for clinical use of EUTCD-grade lines. In particular the UKSCB will seek to:
a) Continue to improved reproducibility of qualified methods for culture expansion, characterisation and cryopreservation of hESC cell lines including naïve hESCs and those from gene edited embryos
b) Implement better defined banking conditions for clinical grade stem cells lines on synthetic culture surfaces
The second UKSCB research theme on standardisation and safety will:
a) Establish, as part of a NIBSC-led work-stream, a robust and internationally acceptable advanced risk assessment process for vCJD contamination of stem cells together with detection protocols for EUTCD-grade lines
b) Develop methods and reference materials to assist in establishing metrics for reproducibility and acceptability of stem cell cultures.
4) To utilise maintain close collaboration with cutting edge researchers and key industry partners to leverage delivery of UKSCB scientific objectives for the benefit of UK regenerative medicine and ensure the UKSCB maintains its reputation as the premier source of high quality stem cell lines for clinical application.
5) To deliver an ongoing programme of training, workshops and advice based on UKSCB and NIBSC expertise in stem cell bioprocessing and regulatory science.
6) To develop a wider programme of communications to enhance connectivity with the stem cell and regenerative medicines communities.

The UK Stem Cell Bank (UKSCB) at NIBSC supports UK regulation on research use of human embryos and makes human embryonic stem cell lines available for international research and clinical use as a public resource. The UKSCB activity to date has created a world-class resource centre from which to obtain high quality stem cell lines, scientific collaboration and advice on the early stages of developing regenerative medicines. The UKSCB has established a reputation and broadened its impact in regenerative medicine, including its support for industry, regulators and policy makers. It now proposes to focus on the preparation and distribution of seed stocks of hESC lines suitable for use in clinical trials under European regulation. This will also require state of the art characterisation, quality control and safety testing of stem cell cultures. The UKSCB will also sustain its support for the regenerative medicine community, including training for a cohort of regulatory scientists to support translational research programmes.
It is crucial to its mission that the UKSCB is equipped to sustain its resource of materials and expertise, to assure international acceptability and relevance of its output to rapidly developing science and technology. This will be achieved through a coordination of new NIBSC-MHRA regulatory science work-streams (e.g., vCJD detection, expanded genetic datasets) and infrastructure support for the UKSCB project. This will also be supported by supplementary grant applications that will facilitate closer scientific partnerships within the UK regenerative medicine infrastructure and enhance national coordination and governance. This approach will be vital to ensure that the substantial investment made by MRC and BBSRC in the UKSCB provides ongoing benefit to sustain, promote and develop the UK position in advanced therapies, by equipping the UKSCB to address future regulatory science demands for advanced therapies.

Academic research using quality-controlled UKSCB cell lines will avoid the significant risks of wasted resources and invalid research arising from work performed on unauthenticated and contaminated cultures which are known to have been circulated via research laboratory supply chains. In addition, researchers will have the opportunity to carry out research on UKSCB EUTCD-grade cell lines, which means research outputs can be taken forward more rapidly to clinic. Researchers seeking to use stem cells for different disciplines, may not be initially well trained in cell culture, and will also benefit from the availability of UKSCB advice and protocols for cell culture, preservation and characterisation.
Developers of hESC-based therapies will have access to cell lines, derived in licensed facilities, which have also been proved through the UKSCB due diligence process for ensuring EUTCD compliance of each individual cell line. This will reduce risk to both patients and commercial developers and give a solid starting point for numerous products thus saving resource to progress to clinical trial and market authorisation. Where developers are using common cell lines from the UKSCB source, a growing history of safe use, coming from multiple applications for the same lines, will enhance regulatory confidence and promote rapid progress to clinic. These benefits will be of paramount importance in an area of complex and diverse regenerative medicines where the timelines from research discovery to first-in-man studies are ever-shortening, with less time to fully understand the systems being used, their modes of action, the crucial safety signals and predictors of efficacy.
The UKSCB will promote progress in regenerative medicine and the utility of stem cell lines for research by the dissemination of protocols, controls and publications on regulatory science and best practice via its strong network of national and international contacts in the pharmaceutical industry, academic research networks, regenerative medicine trade organisations (e.g. FIRM, ARM), health services, testing companies and academic consortia. The UKSCB also impacts on commercial development through beta testing of new technologies and products; where the Bank's expertise in a broad range of hPSCs, and its recognised ability to troubleshoot and investigate the suitability of raw materials from a risk and quality perspective, continues to be important to reagent and media suppliers.
The Bank and NIBSC also gives open access to provide expert advice in the field of regenerative medicine to regulatory bodies (e.g. MHRA, EMA, USFDA and WHO), UK and US funding bodies and policy setting groups (e.g. UK DH, Japanese and Korean authorities), charities (e.g. AMRC), patient lobby groups, and the media.
The UKSCB, plays a key role in coordinating UK derivers and users of EUTCD-hESC lines through its leadership of workshop meetings of stakeholders (see proposal, section 4.4) and international fora (see proposal section 4.4) which provides regulatory and scientific support to more than 20 countries on best practice in stem cell bioprocessing an governance for both research and clinical application. The UKSCB's strong international networking (see Appendix 2) also provides a current and growing benefit to members of the UK regenerative medicine community through introductions to foreign researchers and companies with potential benefits of collaboration and inward investment.
UKSCB disseminates its know-how through scientific publications and reviews, but also importantly via practical training, through annual courses (e.g., EBiSC, Harvard Stem Cell Institute,) and assisting in initiating the new courses (HipSci/ Wellcome Trust advanced course in iPSC culture). This is a particularly important role which is helping to educate a new generation in translational science.