Cardiff Fetal Tissue Bank: Quality assured tissue for biomedical research and clinical trial in neurodegenerative disease

The CFTB and SWIFT tissue banks collect human fetal tissues from the tissue products resulting from elective termination of pregnancy ("abortions"). In the consent process, the purposes of our research programmes to develop new therapies for patients with degenerative brain diseases are fully explained, and the women are asked to donate their tissues to these research programmes. The informed consent procedures are approved by the national research ethics service.
The principal difference between the two banks lies in the purposes for which tissue is collected, and hence the degree of sterility of the processes used. The SWIFT tissue bank operates to "research grade" procedures for safe handling of research tissues in the laboratory. Collected tissue is then used by ourselves and other approved programmes for a wide range of studies including human brain and body development, understanding the organisation and function of normal cells and organs of the body including brain, lung, kidney, eye and spinal cord, in the culture dish and the development of new therapies by transplantation in animal models of brain, eye and spinal cord disease. A major subset of these programmes focus on understanding the development and differentiation of stem cells into different cell fates appropriate for the next generation of cell therapies.
Conversely, the CFTB operates to "clinical grade" under fully defined sterile procedures, in a rigorously controlled cleanroom environment, and is licenced by the Human Tissue Authority to supply clinical grade cells for "human use" including for cell transplantation in patients with a range of neurodegenerative diseases. At present we are processing fetal brain cells for brain transplantation in clinical trials in Parkinson's disease, to resume trials in Huntington's disease, and preparing to launch a new programme in epilepsy. Each new clinical application requires separate preclinical testing, validation and training in all tissue processes, and separate licencing by the Authority.
Thus the combined CFTB / SWIFT facility provides a unique national resource for supplying high quality research and clinical grade cells and tissues originating from the human embryo, both for fundamental research and for clinical trial use. Although designed to supply our own programmes in primary and stem cell transplantation in neurodegenerative disease, we seek to maximise the utility and value of the facility by supplying specialist tissues to over 20 other research programmes and centres in the UK and Europe.
The impact of the research results from the different studies to which the tissue is put, none of which would be possible without the quality-assured infrastructure to supply the source tissues that the CFTB/SWIFT provides.

The CFTB and SWIFT tissue banks provide a combined infrastructure facility to supply quality assured research grade and clincial grade human fetal tissues to support basic, translational and clinical trial applications. Both Banks recruit donors consented for medical and surgical terminations of pregnancy between 6-14 week of fetal development. Tissues are allocated to one of two streams, for processing either under standard cat II human tissue safety protocols in the laboratory for research use (SWIFT), or under GMP in a dedicated clinical grade clean room with appropriate environmental control, monitoring, standardised operating procedures, training, documentation and quality assurance protocols licenced for human use (e.g. cell transplantation) in man (CFTB). The two banks are fully accredited under HTA research and human use licences, respectively.
Whereas the facility was established to support our own programme in cell transplantation in Huntington's and Parkinson's diseases, this is a unique facility providing a rare and valuable resource, and we seek to maximise utility by operating as a fresh fetal tissue bank to supply diverse research programmes in developmental and stem cell biology, immunology and cell transplantation throughout the UK and Europe. We are currently supplying quality assured tissues to approx. 20 other centres, but there are reasonable expectations that the rapid growth in experimental regenerative medicines and cell therapies will raise a significant range of new applications which we will be positioned to supply, breaking an intrinsic bottleneck in the difficulties of sourcing new supplies of this sensitive tissue source.
The SWIFT/CFTB supply is of fresh fetal tissue, in which the cells are living and exhibit high viability for in vitro growth and expension, and are already being used as a source of cells for generation of clinical-grade iPS cells derived from developing fetal brain. As such, we do not compete with the HDBR.

Who will benefit from this research:

i. Patients. The main beneficiaries are expected to be patients and their families. The SWIFT and CFTB facilities provide infrastructure to deliver basic, preclinical and direct translational research in neural transplantation for neurodegenerative disease. The first beneficiaries are likely to be patients with Parkinson's and Huntington's disease. The present first generation trials are using primary fetal cell in which we are establishing the principles and protocols of effective cell transplantation to achieve effective and sustained functional recovery, using the only cells currently available that have validated safety, specificity, growth and integration potential, ie primary fetal neural tissues. This is likely to be followed by various renewable cell sources, including expanded fetal progenitors, that yield a sufficient number of cells for bilateral multisite implants in a single patient from a single donor. This is expected to be superceded in turn by a range of ES- and iPS-derived neurons for which the science is rapidly approaching readiness for clinical trial (while not underestimating the reliability, safety and validity criteria that are likely to be required in the present regulatory environment). Moreover, whereas our own programme will continue to focus on basal ganglia disease, new protocols are in rapid development across a range of other applications, including epilepsy, multiple sclerosis, retinal disease, spinal cord injury, and dementia. However, without an appropriately licenced facility to supply quality assured source materials, and the trained and experience staff operating to validated protocols able to do so rapidly and efficiently, translation of each new opportunity into the clinic will be severely compromised.

ii. Commercial interests. Because of its "one hit" rationale to achieve a lifetime benefit, regenerative medicine continues to provide a challence for commercial business models, and alternative strategies for licencing and delivery of cell based therapies are much debated. The clearest strategies lie in licencing specific cell preparation, specification and differentiation protocols, specialist clinical grade media, and large scale expansion and differentiation of stem cells into multiple mature phenotypes for high throughput drug screening and toxicology, rather than marketing therapeutic cells themselves for neurosurgical transplantation. We interact closely with both small biotech and large pharma (esp. Pfizer and GE Healthcare) in tracking and seeking to exploit this emerging landscape, although specific opportunities remain to be identified.

iii. Politicians and regulators. Being based in Cardiff and located immediately adjacent to the Welsh Government buildings in Cathay's Park, we have a much closer rapport with the health arms of the devolved government and civil service than is typical for central UK government in London. We meet regularly with members of the administration for the Welsh Department of Health and Social Welfare, and NISCHR, its health research arm, as an ad hoc source of information on current topics such as stem cell science, ethics and support. We have undertaken several formal presentations within the Welsh Senedd, including to Assembly Members. Maintaining these links is important for promoting the development of a vibrant research environment in Wales, and our authority is massively enhanced by continued MRC major funding for our own research.

iv. Public and social policy. Stem cell therapy and cell transplantation in the human brain are both topics of widespread public interest and fascination, and our research involves a range of controversial technologies. We have an important responsibility to engage in the public debate to ensure that these powerful new scientific technologies are adopted ethically and legally to individual and public benefit, with social approval, and under full ethical scrutiny.