Stem cell scientists at King's College London will today (Tuesday 6 December) announce they have submitted to the UK Stem Cell Bank (UKSCB) their first clinical grade human embryonic stem (hES) cell lines that are free from animal-derived products, known as 'xeno-free' stem cells.
The cells, which have the potential to become the 'gold standard' lines for developing new stem cell-based therapies, will be the first deposited in the UKSCB based at the National Institute for Biological Standards and Control, under arrangements that will ensure they are freely accessible to the wider research community. The expectation is that these cells will be grown and processed by the UKSCB to provide stem cell stocks that will be used for clinical research and treatment to benefit patients.
Researchers say this is a significant milestone; this first batch of cells is the culmination of nearly ten years of research funded strategically by the Medical Research Council (MRC) that will keep the UK at the forefront of regenerative medicine.
Embryonic stem cells can be grown in the laboratory indefinitely while retaining their capacity to develop into specialised cell types, such as nerve or heart muscle cells, which can then be used in clinical trials. More than 20 'research grade' stem cell lines have been provided by King's to the UKSCB since it derived the first research grade hES cell lines in the UK in 2003, but the challenge to date has been to establish appropriate derivation and growing conditions for the cells without the presence of any animal products, such as porcine enzymes, bovine serum or mouse feeder layers.
Clinical use of hES cells is already being explored in a number of phase 1 safety trials, such as spinal cord injury and macular degeneration. However, the hES cell lines used in these trials were reclassified from 'research grade' to 'clinical grade' for specified short-term clinical studies in selected disease states, as a matter of expediency. This route is not considered appropriate for the future of cell therapy because of the expense of the required testing and reclassification, and the significant risk of using cell lines derived on unqualified feeders, using unqualified reagents under undocumented environmental conditions in the embryology and stem cell labs and storage facilities. While it might be reasonable to incur additional risks for these early pioneering studies, it is not reasonable to accept these risks for the long-term future of cell therapy. Therefore the highest standard of xeno-free lines are urgently needed, and the development of these lines by King's represents a major step forward.
The hES cells were grown from frozen embryos donated by patients who had previously undergone IVF treatment and no longer wished to use their remaining stored embryos. These embryos would otherwise have been discarded in line with HFEA requirements.
The work took place in the purpose-built stem cell laboratory at King's, in collaboration with the Assisted Conception Unit at Guy's and St Thomas' NHS Foundation Trust, as part of King's Health Partners Academic Health Sciences Centre, and licensed by the Human Fertilisation and Embryology Authority (HFEA) and the Human Tissue Authority (HTA). The laboratory is compliant with Current Good Manufacturing Practices (cGMP).
The team developed a comprehensive methodology and standards for derivation of the xeno-free hES cell lines that will be appropriate for studies in human subjects after suitable additional testing and processing by the UKSCB. Developed in line with these rigorous standards, researchers, physicians and industry can be reassured of the reliability of the seed stock – the essential base for translational applications. It is hoped that these standards will be recognised across academia, future users and policy agencies operating in and monitoring the field.
As the research that underpinned this work was funded by the MRC, the decision has been taken to submit these to the UKSCB for open-access therapeutic use for the public good. A number of additional xeno-free lines will follow shortly from King's and from the stem cell team at the University of Manchester/Central Manchester NHS Trust, who have been similarly supported by MRC and have also developed clinical grade hES cells to submit to the UKSCB in the same way.
Professor Peter Braude, Emeritus Professor of Obstetrics and Gynaecology, King's College London; former director of the Stem Cell Programme and the Pre-Implantation Genetic Diagnosis Programme, Guy's and St Thomas' NHS Foundation Trust, said:
'This is a significant achievement of the team, one which we have been working towards for many years with the support of the University, our local hospital, and most importantly the Medical Research Council. We have succeeded where many substantial commercial companies have not. Many more xeno-free lines should follow, which demonstrates the validity and foresight of this and previous governments in this important endeavour.'
Dr Dusko Ilic, Senior Lecturer in Stem Cell Science at King's, said:
'I'm pleased that we have finally been able to supply the UK Stem Cell Bank with well-characterised hES cell lines for public use, and can therefore contribute to the ongoing consolidation of the UK as a leading international player in the stem cell field. In the future, patients hoping for the benefit of regenerative medicine for serious medical conditions caused by illness, injury and ageing, can expect improved progress on cures or amelioration from hES cell-based therapy.'
Dr Rob Buckle, Head of Regenerative Medicine at the MRC, said:
'The MRC is delighted that this investment into regenerative medicine research is beginning to bear fruit. The development of xeno-free hES cells lines is a major step forward in the field as it paves the way for 'gold standard' clinical-grade cell lines suitable for use in humans. This is essential in demonstrating proof-of-concept for stem-cell therapies, which have the potential to treat many diseases that currently have no effective cure. Furthermore, the distribution of these high quality and ethically-sourced lines through the UK Stem Cell Bank will ensure these are widely available to the research community as we seek to accelerate progress in this area.'
Dr Glyn Stacey Head of the UK Stem Cell Bank, based at the National Institute for Biological Standards and Control, a centre of the Health Protection Agency, said:
'These lines will be an important resource to fulfill our plan to make available a panel of characterised and tested clinical grade lines within the next three years. The process of testing will be rigorous and not all cells lines received will make the grade. We will need significantly more lines submitted to reach these targets, especially those that are to be made available for universal use.'
Professor Daniel Brison, Scientific Director of the IVF unit at St Mary's and Co-Director of the Manchester stem cell group, said:
'This is the first step towards a number of clinical lines from King's and from ourselves which should reframe and enhance the initiative established in the UK, and lead the way to important new therapies in regenerative medicine.'
Notes to editors:
An early online paper on the methodology and standards developed by King's College London for the derivation of xeno-free hES cells is available from Cytotherapy, the official journal of the International Society for Cellular Therapy (http://www.celltherapysociety.org) http://www.ncbi.nlm.nih.gov/pubmed/22029654
King's College London
King's College London is one of the top 30 universities in the world (2011/12 QS World University Rankings), and the fourth oldest in England. A research-led university based in the heart of London, King's has nearly 23,500 students (of whom more than 9,000 are graduate students) from nearly 140 countries, and some 6,000 employees. King's is in the second phase of a £1 billion redevelopment programme which is transforming its estate.
King's has an outstanding reputation for providing world-class teaching and cutting-edge research. In the 2008 Research Assessment Exercise for British universities, 23 departments were ranked in the top quartile of British universities; over half of our academic staff work in departments that are in the top 10 per cent in the UK in their field and can thus be classed as world leading. The College is in the top seven UK universities for research earnings and has an overall annual income of nearly £450 million.
King's has a particularly distinguished reputation in the humanities, law, the sciences (including a wide range of health areas such as psychiatry, medicine, nursing and dentistry) and social sciences including international affairs. It has played a major role in many of the advances that have shaped modern life, such as the discovery of the structure of DNA and research that led to the development of radio, television, mobile phones and radar. It is the largest centre for the education of healthcare professionals in Europe; no university has more Medical Research Council Centres.
Assisted Conception Unit at Guy's and St Thomas' NHT Foundation Trust
The Assisted Conception Unit has world-leading expertise in the field of fertility and pre-implantation genetic diagnosis, and an international reputation for excellence and research. Guy's and St Thomas' is one of the biggest NHS Trusts in the UK, providing a million patient contacts in acute and specialist hospital services every year. http://www.guysandstthomas.nhs.uk
King's Health Partners
King's College London and Guy's and St Thomas', King's College Hospital and South London and Maudsley NHS Foundation Trusts are part of King's Health Partners. King's Health Partners Academic Health Sciences Centre (AHSC) is a pioneering global collaboration between one of the world's leading research-led universities and three of London's most successful NHS Foundation Trusts, including leading teaching hospitals and comprehensive mental health services. For more information, visit: http://www.kingshealthpartners.org.
Medical Research Council
For almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. http://www.mrc.ac.uk
The Health Protection Agency
The Health Protection Agency is an independent UK organisation that was set up by the government in 2003 to protect the public from threats to their health from infectious diseases and environmental hazards. In April 2013, subject to the usual approvals procedures for establishing new bodies, the Health Protection Agency will become part of a new organisation called Public Health England, an executive agency of the Department of Health. The National Institute for Biological Standards and Control (NIBSC), a centre of the HPA, is the global leader in the field of biological standardisation, responsible for developing and producing over 90% of the International Standards in use around the world to assure the quality of biological medicines. The UK Stem Cell Bank (UKSCB) was established at the NIBSC to provide an ethically sourced repository of human embryonic, foetal and adult stem cell lines as part of the UK governance for the use of human embryos for research. Its role is to provide quality controlled stocks of these cells that researchers worldwide can rely on to facilitate high quality and standardised research. It is also ready to prepare stocks of 'clinical grade' cell lines as seed stocks for the development of therapies. UKSCB provides an international leader in banking human stem cell lines and plays a key role in numerous European and broader international stem cell research projects. The UKSCB provides stem cell lines and other research reagents but does not supply human tissues or cord blood. To find out more, visit our website: http://www.hpa.org.uk or follow us on Twitter@HPAuk.