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

Lead Research Organisation: Cardiff University
Department Name: School of Biosciences

Abstract

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.

Technical Summary

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.

Planned Impact

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.

Publications

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Dunnett SB (2017) Reprogramming the diseased brain. in Nature biotechnology

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Martín-Ibáñez R (2017) Insights in spatio-temporal characterization of human fetal neural stem cells. in Experimental neurology

 
Description Stem cells for HD (SC4HD)
Geographic Reach Multiple continents/international 
Policy Influence Type Influenced training of practitioners or researchers
 
Description A device for delivering stem cell therapies to the human brain
Amount £74,812 (GBP)
Funding ID Co-applicant 
Organisation European Social Fund (Welsh Government/ EU) 
Sector Public
Country United Kingdom
Start 05/2017 
End 03/2018
 
Description Brain Repair and Intracranial Neurotherapeutics - the Wales BRAIN Unit
Amount £800,000 (GBP)
Organisation Welsh Assembly 
Sector Public
Country United Kingdom
Start 04/2018 
End 03/2020
 
Description Developing stem cell technologies for the neurodegeneration of Alzheimer's disease: Assessing the capacity of embryonic stem cell-derived projection neurons and interneurons to integrate in adult cortex
Amount £150,000 (GBP)
Organisation Campaign for Alzheimer's Research in Europe 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2017 
End 09/2019
 
Description Fetal derived iPS cells as a source of donor cells for a regeneration medicine approach to treating Huntington's disease
Amount £36,875 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 10/2015 
End 03/2017
 
Description TRial designs for DElivery of Novel Therapies for Neurodegeneration (TRIDENT)
Amount £184,128 (GBP)
Funding ID RfPPB-16a-1298 
Organisation Health and Care Research Wales 
Sector Public
Country United Kingdom
Start 10/2017 
End 09/2019
 
Description Training on advanced stem cell technologies in neurology
Amount £484,652 (GBP)
Funding ID 813851 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 10/2018 
End 12/2023
 
Description EU FP7 Transeuro 
Organisation University of Cambridge
Department John van Geest Centre for Brain Repair
Country United Kingdom 
Sector Academic/University 
PI Contribution supply of cells and protocols
Collaborator Contribution collabortive experiments
Impact collaborative clinical trial
Start Year 2010
 
Description Eurostemcells 
Organisation EU-T0
Country European Union (EU) 
Sector Public 
PI Contribution Eurostemcells is an educational Consortium to provide reliable information about stem cells and their application including their impact on society. My/my team contribute articles, edit reports and information leaflets.
Collaborator Contribution Coordinated by University of Edinburgh.
Impact Information and reports
Start Year 2014
 
Description O&G/UHW 
Organisation University Hospital of Wales
Country United Kingdom 
Sector Hospitals 
PI Contribution Ongoing collaboration with O&G fundamental to our consented ethical collection of human fetal tissues. Processing, preparation, and validation in vitro and in vivo of cell and tissue viability and potential for functional repair
Collaborator Contribution Ongoing collaboration with O&G fundamental to our consented ethical collection of human fetal tissues.
Impact Recent major development in identification of mTOPs as new source of fetal tissues for research and therapy.
 
Description Repair-HD 
Organisation EU-T0
Country European Union (EU) 
Sector Public 
PI Contribution Coordinator of the Consortium, transplantation into rodents, development of clinical assessment tools for behavioural and functional assessment, observational patient study.
Collaborator Contribution Development of cell protocols, transplantation into primate models, manufacture of GMP grade cells, development of assessment tools for cognitive and motor assessment.
Impact Publications, differentiation protocols, clinical assessment tools
Start Year 2013
 
Description EHDN plenary 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Discussion with scientists, clinicians and also with patients. Has led to further invitations to speak at meetings.
Year(s) Of Engagement Activity 2016
 
Description HD regional public engagement event 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Discussion with patients and carers about pace and challenges of cell replacement therapy.
Year(s) Of Engagement Activity 2016
 
Description NECTAR 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Discussion and development of research plans.
Year(s) Of Engagement Activity 2016
 
Description Presentation at stem cell meeting in Oxford 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Oxford stem cell meeting. Stimulated discussion which led to a change in ongoing experimental program.
Year(s) Of Engagement Activity 2016
 
Description Presentation at undergraduate medical society meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Undergraduate students
Results and Impact Keynote speaker at Cambridge medical student one day meeting. Interaction and discussion with medical students from Cambridge region.
Year(s) Of Engagement Activity 2019
 
Description Presentation to final year medical students 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact approx 40 undergraduate and graduate medical students. Precipitated discussion which continued after the formal presentation. Have had follow-up enquiries from medical students asking to work in Brain Repair Group.
Year(s) Of Engagement Activity 2016
 
Description Repair-HD public engagement event Wales, Pierhead 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Policymakers/politicians
Results and Impact The event was sponsored by a Wales Assembly member and was advertised to policy makers, patients, carers, professionals and the public. The program was focused on new treatments for HD, in particular cell replacement therapy, but also including gene therapies. Around 100 people attended and substantial discussion was stimulated. I have been approached by patients, carers and colleagues in the following months with further questions and comments.
Year(s) Of Engagement Activity 2017
 
Description Swiss society neuroscience 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Postgraduate students
Results and Impact Discussion with postgraduate students/
Year(s) Of Engagement Activity 2017
 
Description Talk to Chinese neurological Society in Guangzhou 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact Presented current status of Cell therapy for Huntingtin's disease. The talk stimulation a lot of questions and I was approached by several audience members saying that it had changed their views of regenerative medicine for neurodegenerative disease. It has also led to a further invitation to present at the Movement Disorder conference in Hong Kong.
Year(s) Of Engagement Activity 2017
 
Description Talk to Parkinson's patient group in Hing Kong 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Patients, carers and/or patient groups
Results and Impact Talk to Parkinson's patient group in Hong Kong consisting of approximately 100 patients, carers, with some professionals, third sector etc. The talk was to explain the place of cell therapies in PD and resulted in a substantial number of questions from the audience.
Year(s) Of Engagement Activity 2018