Derivation of clinical grade embryonic stem cell lines

Human embryonic stem (hES) cells can be isolated from early (6 day old) developing embryos which have been grown in the laboratory as part of, or surplus to some kinds of IVF treatment. Under certain conditions, these cells can be made to develop into different kinds of tissues, such as nerve cells or pancreatic cells which it is hoped in the future, may be useful in treating degenerative diseases such as Parkinson s disease and diabetes, or in spinal injuries by replacing the diseased or damaged cells with healthy hES cells which have been grown in the laboratory. The number of hES cell lines that have been developed worldwide that are suitable for clinical use is still very limited. Further research is required to find out the best means to grow them in ways that will allow them to be safe for clinical use which is the purpose of this grant. All stem cell derivation from embryos is strictly monitored in the UK and requires a licence from the Human Fertilisation and Embryology Authority (HFEA). In compliance with conditions of our HFEA licence, samples of any suitable stem cell lines developed will be sent to the UK Stem Cell Bank from where they are made available to research scientists in the UK and abroad through the MRC Stem Cell Steering Committee, and if suitable, for further preparation in the UKSCB for clinical use. With the Assisted Conception Unit (ACU) at Guy s, we have developed ethical ways of obtaining embryos for deriving stem cell lines that may be suitable for clinical use, especially from couples who have successfully undergone IVF treatment and have additional embryos in frozen storage which they no longer wish to use in their own treatment, nor wish to donate to other individuals. Rather than destroy them, patients often prefer to donate them for stem cell or other worthwhile research.

The development and support of the UK stem cell bank is a clear signal of the government?s commitment to support both local and international research in stem cell research, and to the development of lines suitable for clinical use.
Although there have been important advances in the generation of hES, the derivation of lines for human use is tempered by the stringent requirements and methodological changes needed to meet GMP production standards. These include unequivocal permission from embryo donors for use of their embryos for therapeutic purposes without restrictions or financial claim, clear provenance of embryos including history, infectious agent of the donors, and documentation assuring traceability through the various stages from fertilization, though culture to blastocyst, and where indicated, cryopreservation. There also need to be changes to the methods for isolation of inner cell masses from blastocysts, moving away from the animal feeder layers for derivation and growth, and the use of more clearly defined media free of animal products.
Key to successful hES generation is access to human embryos in vitro able to develop to the blastocyst stage and beyond, and suitable facilities to derive under conditions compliant with the EUTCD and the requirements of the HTA. Ethical access to good quality embryos has been facilitated through the large and successful assisted conception unit and PGD programme at Guy s Hospital where over 1000 cycles are performed annually. In addition, through our nurse coordinator funded by MRC, we have set up a strong collaboration with 9 local NHS and private IVF units to provide cryopreserved embryos surplus to patients therapeutic need and suitable for stem cell research. We have also secured an investment of #4m from the MRC, KCL, the Guys and St Thomas? Charity and the Trust, towards the build of a new assisted conception unit on the 11th floor of the Guy?s tower, to house IVF treatment facilities, PGD laboratories and a two-room GMP stem cell suite leading directly off the IVF laboratory, due for completion in July 2008. It is our intention to utilise these facilities to generate, grown and characterise under GMP conditions, embryonic stem cell lines suitable for deposit in the UK Stem Cell Bank as clinical grade lines. In response to this strategic call we are applying for staff, equipment and supplies to enable us fulfill this aim.