UK Stem Cell Bank Application for Phase IV Funding 2014 - 2017

Our growing understanding of the biology of human pluripotent stem cells (hPSCs) provides unprecedented opportunities to generate cells to repair or replace any cell-type for large numbers of patients with traumatic injury, genetic defects and degenerative diseases. It also provides researchers with a powerful research tool to develop human tissue models to study human disease, develop new drugs and investigate their safety. The pathway to deliver these advances in basic science and medicine in an efficient and robust way is to establish a solid structure that starts with ethically sourced, reliable and appropriately characterised source materials (cells and controls). It also requires methodologies to enable key scientific and medical developments to feed a pipeline for new medical products and novel applications of stem cells. A key function of UKSCB in the UK regenerative medicine programme will be to make available carefully prepared and tested stocks of ethically sourced human stem cell lines, produced in the UK specifically for clinical use. The UKSCB will prepare these as a centralised UK resource of well characterised human embryonic stem cell (hESC) banks for cell therapy (i.e. compliant with UK and European regulation) and make them available to the UK and international cell therapy community. Stem cell lines with a range of genetic and physical characteristics of value to researchers will also be banked and made available by UKSCB to the international research community. This banking programme will also support the research community by releasing stocks of its own feeder cells to use in routine stem cell culture. The UKSCB will also deliver a translational research programme focused on 1) improving banking processes and 2) standardisation and safety issues for clinical use of stem cell cultures. The first theme in UKSCB research will enhance its cell banking function through i) optimisation of methods for culture expansion, characterisation and cryopreservation of stem cell lines, and ii) generation of new human feeder cells for culture of clinical grade stem cells lines. In the second theme on standardisation and safety, UKSCB will use cutting edge genome sequencing techniques to develop screening methods for microbial agents and mutations in clinical grade cells and also develop methods and control materials to assist in establishing metrics for reproducibility and acceptability of stem cell cultures for use. The research planned under core MRC funding for the UKSCB will be supported by existing collaborations with additional funding and will be expanded significantly (particularly in automation and improving stem cell characterisation) through new grant applications currently under evaluation. Other work will include an active programme of training, education and advice based on the UKSCB's experience and expertise in stem cell culture, preservation, characterisation and regulatory issues. This will be developed with supplementary funding obtained through collaboration with other stem cell banks and stem cell research institutes in the UK and abroad. The UKSCB international profile will be maintained and developed through active engagement with researchers and stem cell banks in other countries and its leadership in stem cell banking and regulatory science issues for cell therapy. This will be used to facilitate links between foreign laboratories and companies and the UK regenerative medicine community to promote collaboration and inward investment. In conclusion, the UKSCB proposal will provide fundamental component of UK regulation on the use of embryos which has gained the UK a reputation for solid and robust ethical regulation. In addition, it will ensure there is vital underpinning support on technical, safety and ethical issues that is critical for the early stages of translation of research methods into 'first in man' studies to assure a safe and secure pathway to new cell therapies.

The Bank will work closely with UK derivation centres to procure hESC lines, assure their compliance with UK and EU regulation and produce a panel of well characterised hESC banks and feeder cells for use in humans (i.e. EUTCD-hESCs). In addition, the Bank will continue to develop its panel of research grade hPSCs, focussing on those with greatest value in research, including a set of reference cell banks (RCBs) of hESC and hiPSCs. The process of banking will be streamlined and flexibility increased by the automation of aspects of banking and characterisation. The Bank will generate quality controlled, safety-tested human diploid fibroblasts as starting materials for a reference panel of hiPSCs to be developed by the Bank using a range of reprogramming methodologies.
RCBs and EUTCD-hESCs will be subjected to investigation of their genomic and phenotypic characteristics, stability on extended passage and microbiological safety. Data will be published on the Bank's website and other research databases to enhance the value of these cell lines to researchers and provide important information on the suitability of EUTCD-hESCs for clinical use. The Bank will also develop generic regulatory science approaches and control materials for standardisation of hPSCs for use in establishing cell therapies. Its R&D will be coordinated with leading researchers and NIBSC scientists in a programme of research projects funded from a variety of sources. It will maintain an active programme of training and advice for industry and research. In summary the UKSCB Phase IV proposal provides a well-rounded programme of supply of important research materials, well-characterised and qualified starting materials for development of cell therapies, underpinning method development for application in hPSC-based medicines and a training, advisory and external coordination programme to facilitate the development of the UK regenerative medicine and promote robust and high quality stem cell research.

The beneficiaries of the UKSCB's focus on banking of Clinical Grade hESCs and underpinning research in regulatory science of stem cells will be both the clinical and industrial research communities. They will benefit from the quality-controlled Laboratory Grade cell lines (thus avoiding the serious risk of contaminated or misidentified cell lines) as well as the safety-tested EUTCD-Grade cell lines suitable for clinical trial, where availability of traceable, well documented, reliable and appropriately qualified stocks of cells will be paramount from a regulatory and patient health perspective.
The UKSCB already has strong links with commercial organisations such as GSK, Roslin Cells, Asymptote, Apopro, and GE Healthcare through existing and proposed research collaborations. Other strong links have evolved with suppliers such as TAP, Stem Cell Technologies and LifeTechnologies through beta testing of new technologies, 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 provides 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.
In addition the UKSCB is actively engaged with key UK government funded organisations (e.g. Cell Therapy Catapult Centre, NHSBT, UK Biobank) and many of the UK stem cell centres, including Stem Cell Institute (University of Cambridge), HiPSC (Sanger Institute), and the Centre for Stem Cell Biology (University of Sheffield), in helping to consolidate the UK infrastructure in support of regenerative medicine. It also provides expertise to the regional networks (e.g. Manchester Tissue Regeneration and Stem Cell Network, Regener8) and other research consortia in the UK (e.g. UKRMP hubs, Stem Cells for Safer Medicine). Within Europe the Bank also impacts on research, through its involvement in EU framework 7 consortia such as ESNATS, Scr&Tox, Seurat-1, StemBANCC, ToxBank and ISCF funded ISCI.
The UKSCB, through its participation in, or leadership of, both UK (e.g. National Clinical human Embryonic Stem Cell Forum) and international (e.g. International Stem Cell Banking Initiative) forums provides regulatory and scientific expertise to more than 20 countries on best practice in the culture, characterisation and banking of stem cells for both research and clinical application. The UKSCB's strong international networking 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.
The UKSCB's role in providing advice and practical training, through for example its joint course with the Harvard Stem Cell Institute, will benefit new researchers in the stem cell and regenerative medicines field; providing them with the crucial scientific and technical knowledge in the use of stem cell lines. This will have an ongoing, and potentially growing, impact as new fields of research begin to use stem cell lines in their research. Those academics, clinicians and industrial partners working at the early translational phase between basic research and clinical implementation can obtain immediate and valuable benefit from the UKSCB's technical knowledge (built over ten years), its independent and neutral advice on regulatory issues and its capabilities in regulatory science. This will facilitate the avoidance of critical problems and help smooth the path to safe and effective cell-based medicines over the next ten years and beyond for both hESC-derived cellular therapies and the nascent field of hiPSCs.