The Pluripotent Stem Cells and Engineered Cell (PSEC) Hub

Lead Research Organisation: University of Cambridge
Department Name: Clinical Neurosciences

Abstract

The ability to repair the injured or diseased human body with human pluripotent stem cell (hPSC) derived products is emerging as a realistic therapeutic option. However this brings with it a number of major challenges;
1) Can this be done safely?
2) Can this be done usefully and competitively? i.e. it the treatment as good or better than what is available; and
3) Can we do this at the scale needed to treat all patients that might require this type of therapy?

In this new hub we will work on these issues around two particular therapeutic agents. The first involves making dopamine nerve cells to replace those lost in the brain of patients with Parkinson's disease (PD). The second involves making a specific component of blood that is vital for clotting- namely platelets generated from hPSC-derived megakaryocytes. These two cell products and the diseases linked to their use are not seen as the primary output of this grant, but rather will serve to contextualise our work, which is primarily designed to build a platform by which any hPSC-derived therapy can be brought to the clinic. We have three major aims:

The first relates to acquired genetic changes seen in cells grown in the laboratory and what this means for the safety of our hPSCs/cell products. Every cell has DNA, which contains all our genes, and between cells, there will be natural variations along with random errors and mistakes. Many of these changes are of no consequence, while others may be potentially harmful. The question we need to answer is can we reliably detect the bad genetic variants in the hPSCs and the cells we produce from them, while also recognising those genetic changes that are unimportant and can be safely ignored. This is obviously not an easy question to answer, but what we will do, is look at the changes in the genes in a number of different hPSCs/products and then compare what we find with databases that contain information on the links such genetic changes have to known human diseases and cancers. This will allow us to develop guidelines, which will then hopefully be adopted by the relevant regulatory agencies and applied to any hPSC-derived therapy going to clinic.

Our second aim is to address the major issues related to how we can manufacture our hPSC-derived products in the numbers and quality required for clinical use in large numbers of patients. Currently, many of the protocols we have developed in the lab, work well, but the reagents we use are not of the grade needed for use in patients- so called GMP grade. Thus we will seek to develop the necessary clinically compatible protocols and then work out how we can scale up and scale out the manufacturing of the cells we are interested in developing so that ultimately all relevant patients could benefit from these types of treatment. For some diseases, this will be quite straight forward, as we only need relatively few cells to treat patients- e.g. 500,000 to a million cells for a single patient with PD. In other conditions, we will need millions and billions of cells, such as platelets, and this creates huge challenges for manufacturing. We will therefore work on ways to do this, such that we can reliably and reproducibly do this at the level needed for clinical use.

Our final major aim is to develop new techniques to make our cell therapies work better when transplanted. This will involve two main approaches; (i) Techniques to allow us to make the cells we want more efficiently, i.e. so we can manufacture large numbers of cells from our hPSCs as will be needed to treat patients and; (ii) Silencing critical molecules/proteins in the cells that trigger immune rejection, i.e. so that when the cells are grafted into patients their immune system will react to them less vigorously. This in turn will mean that we can use less aggressive immunosuppressive regimes to stop the grafts being rejected and by so doing reduce any side effects from these drugs.

Technical Summary

We will deliver a platform of technologies and expertise that will enable new human pluripotent stem cell (hPSC) based therapies to more readily enter the clinic. This will be done around 2 major therapeutic areas - hPSC derived dopaminergic neurons and megakaryocytes. These exemplars will contextualise the overarching aim of the hub which is to further understand and develop the next generation of genetic and reprogramming tools needed to allow ANY hPSC-based product to progress to clinic. This will be done through 3 major research programmes: THEME 1 - CELL CHARACTERISATION AND STABILITY: We will assess the phenotypic consequences of specific genetic variants using our clinical exemplars, while also developing sensitive high-throughput detection methods for genetically variant cells. We will the use this information to optimise culture conditions to suppress the appearance of concerning genetic variant, while also producing lists of non-consequential genetic variants that we detect which we will then feed into international guidelines for adoption by relevant regulatory agencies. THEME 2 - IDENTIFYING AND MODELLING KEY DETERMINANTS OF MANUFACTURING OUTCOMES FOR HPSC PRODUCTS AND PROVIDING A REGULATORY ROADMAP: We will address issues to do with manufacturing cells in the quantity and the quality required, for clinical adoption using dynamic process models as well as novel protocols and reagents. This will include a pathway for regulatory integration, to facilitate clinical application and first in human studies. THEME 3 - UNDERSTANDING ROUTES TO DIFFERENTIATION: We will develop a new generation of genetically modified hPSCs with improved differentiation capabilities including purity, cell yield and reduced dependence on expensive media and/or complex cytokine cocktails as well as reducing their immunogenicity such that they can more easily be employed in the clinic without the need for major immunosuppressive anti-rejection therapies and their associated risks.

Planned Impact

The impact of our work has already been discussed in part in the section on "Academic Beneficiaries". In essence the work that will be done in this hub has the potential to enhance and transform the UK landscape around hPSC therapies and regenerative medicine in the broadest possible sense.

The hub will generate outputs that will define the significant acquired genetic changes seen in hPSCs and their products and what this means. This will then be used by regulatory agencies to develop guidelines that are likely to be adopted worldwide. This will impact on all hPSC based therapies being developed for clinical use anywhere in the world where there exists an overseeing national agency - e,g, MHRA; EMA, FDA and so on. Furthermore we will also start exploring not just the acquired genetic variation that comes with growing and differentiating these cells, but how this can be better controlled, especially during any manufacturing process and storage of the derived cell products. Finally we will start to explore this at the level of the epigenome which is likely to represent the next level of regulatory scrutiny as more of these cells move into the clinical space.

The second major impact will be in the undertaking of new clinical trials with hPSC derived products and how this can best be done using the emerging genetic engineering and differentiation protocols that have been developed in recent years. The ability to do this in the research lab is well established, but how this can then be done using clinical grade cells, that need to be made reproducibly in a GMP facility, is still unknown. We will address this issue which will impact on any group wishing to adopt similar strategies with their cell products. This work in turn will impact on the future treatment of patients with a whole variety of diseases as well how this can best be delivered in the context of the NHS, and the wider medical market, at an affordable price.

The third major impact will be in terms of the UK regenerative medicine landscape and investment both from funding agencies supporting hPSC based product development by academics as well as biotech companies and big pharma, both nationally and internationally. The investment that has already been made by the UK in this area is impressive (National Stem Cell Bank; Cell and Gene Therapy Catapult etc), but the work we propose will make the UK the optimal location for developing and trialling hPSC derived products. Indeed to date, we have already worked with other groups outside the UK who do not have the national framework and initiatives that we do around hPSC therapies, and thus the investment in the regenerative medicine market is likely to become a major growth area in the UK economy going forward driven in part by the work we are doing through this hub. This will become an increasingly important asset in the UK post Brexit.

Finally our work will impact on many other groups. This will include the greater scientific community and especially those scientists working with hPSCs in the future and in particular how they can optimally culture the cells and the way in which they can be best manipulated genetically for therapeutic use. The patients for whom these therapies are being developed will clearly directly benefit from this work which could have a major impact on how these diseases will routinely be treated in the future. This will lead to a wider discussion at the societal level as to how we see such therapies from an ethical and therapeutic perspective, as well as what we are prepared to pay for them and how all these issues can best be discussed and presented.

In summary the programme of work we propose has the ability to significantly change and impact on the UK such that it will be seen as a global centre for hPSC based regenerative medicine, leading the world in how this can best be done in terms of minimising risk while optimising their speed of development for clinical adoption.

Publications

10 25 50
publication icon
Armstrong J (2020) A blueprint for translational regenerative medicine in Science Translational Medicine

publication icon
Baker D (2022) Characterizing the Genetic Stability of Human Naïve and Primed Pluripotent Stem Cells. in Methods in molecular biology (Clifton, N.J.)

publication icon
Buttery PC (2020) Gene and Cell-Based Therapies for Parkinson's Disease: Where Are We? in Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics

publication icon
Cheung M (2022) Systematic Design, Generation, and Application of Synthetic Datasets for Flow Cytometry. in PDA journal of pharmaceutical science and technology

publication icon
Cheung M (2021) Current trends in flow cytometry automated data analysis software. in Cytometry. Part A : the journal of the International Society for Analytical Cytology

 
Description A director of the ISSCR
Geographic Reach North America 
Policy Influence Type Participation in a advisory committee
 
Description ISCI
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a advisory committee
 
Description ISSCR Task Force on Standards in Stem Cell Research
Geographic Reach Multiple continents/international 
Policy Influence Type Contribution to new or Improved professional practice
 
Description Advanced Bioprocess 2
Amount £100,973 (GBP)
Organisation Advanced Bioprocess Services Ltd 
Sector Private
Country United Kingdom
Start 01/2018 
End 12/2018
 
Description Advanced Bioprocess 3
Amount £41,333 (GBP)
Organisation Advanced Bioprocess Services Ltd 
Sector Private
Country United Kingdom
Start 01/2019 
End 12/2019
 
Description Cell Therapy Manufacturing
Amount £192,717 (GBP)
Organisation Advanced Bioprocess Services Ltd 
Sector Private
Country United Kingdom
Start 01/2020 
End 12/2025
 
Description Modelling Pluripotent Stem Cell Manufacture - Industrial Studentship
Amount £130,211 (GBP)
Organisation Advanced Bioprocess Services Ltd 
Sector Private
Country United Kingdom
Start 03/2019 
End 03/2022
 
Description Multidisciplinary approach to design engineered tissue to improve cell transplantation therapy for Parkinson's disease.
Amount £6,000 (GBP)
Organisation UK Regenerative Medicine Platform 
Sector Academic/University
Country United Kingdom
Start 03/2019 
End 04/2020
 
Description NYSCF - Robertson Stem Cell Investigator Award
Amount $1,500,000 (USD)
Funding ID NYSCF-R-156 
Organisation New York Stem Cell Foundation 
Sector Charity/Non Profit
Country United States
Start 01/2020 
End 12/2024
 
Description STEM-PD trial
Amount £994,206 (GBP)
Organisation Novo Nordisk 
Sector Private
Country Denmark
Start 03/2022 
End 03/2027
 
Description Special initiative
Amount £10,000,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 04/2019 
End 04/2024
 
Description Targeting shared mechanisms in metabolic and neurodegenerative disease (Ben Barres Early Career Acceleration Award)
Amount $2,500,000 (USD)
Funding ID 191942 
Organisation Chan Zuckerberg Initiative 
Sector Private
Country United States
Start 01/2019 
End 12/2023
 
Description The Pluripotent Stem Cells and Engineered Cell (PSEC) Hub
Amount £4,095,179 (GBP)
Funding ID MR/R015724/1 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 05/2018 
End 05/2023
 
Description The immunogenicity of stem cells derived dopamine cells and its implications for first in human clinical trials (Parkinson's)(JBCF)
Amount £173,732 (GBP)
Funding ID M654 
Organisation Rosetrees Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2017 
End 08/2021
 
Description Transitioning in vitro platelet production to GMP".
Amount £100,000 (GBP)
Funding ID X527722 
Organisation Defence Science & Technology Laboratory (DSTL) 
Sector Public
Country United Kingdom
Start 03/2020 
End 03/2021
 
Description UKRMP/Immunology: Immunogenecity test platform - in vitro and in vivo
Amount £907,910 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 03/2019 
End 03/2022
 
Title A reference human induced pluripotent stem cell line 
Description Using deep genotyping and phenotyping, we worked collaboratively to compare 8 candidate iPSC lines and select one to serve as a reference cell line for the field. A pre-print describing this cell line has been published, and we are working to easily share the cell line and accompanying whole genome sequencing data via a website that is scheduled to launch in March 2022. 
Type Of Material Cell line 
Year Produced 2021 
Provided To Others? Yes  
Impact The cell line has been shared with nearly 50 laboratories, and is forming the basis of several large gene editing studies at the NIH, Jackson Laboratories, and the Wellcome Sanger Institute. 
URL https://www.biorxiv.org/content/10.1101/2021.12.15.472643v4
 
Title Bioinformatic pipeline for estimating cell frequencies from pools of genetically distinct cells 
Description Pooling genetically distinct cell lines together and culturing them under diverse conditions is a powerful way to understand how the composition of each cell line changes over time. The method takes advantage of the fact that if the whole genome sequences of each cell line in the pool is known, there are many single nucleotide variants (SNVs) that are informative about cell identity. Even if the pool of cells is sequenced at low depth of sequencing coverage (e.g. 1x), enough SNVs can be called to model the likely abundance of each line in the pool. These methods are still being finalised and will be made widely available by publication. 
Type Of Material Technology assay or reagent 
Year Produced 2021 
Provided To Others? No  
Impact The method is being used by our group and another group at the Wellcome Sanger Institute to pursue pooled culture and differentiation studies, in order to map expression quantitative trait loci, as well as understand selective pressures in culture. 
 
Title HSCGP data portal implementation code and documentation 
Description We created a user-friendly online data portal (https://hscgp.broadinstitute.org/hscgp) that enables users with more limited computational expertise to readily search for sequence variants of interest among sequenced hESC lines. For example, a search for TP53 reveals all variants in the gene that were detected in the sequenced cell lines, the names of those cell lines, as well as bioinformatic predictions about the likely consequences of these variants. Search results can be graphically visualized and exported for further analysis in a variety of formats. Specific cell lines can also be interrogated for the presence of variants of interest, and raw sequencing alignments can be visualized via the integrative genomics viewer IGV. 
Type Of Material Technology assay or reagent 
Year Produced 2021 
Provided To Others? Yes  
Impact Dozens of interested groups have visited the GitHub repository, and the code is being implemented as part of the JAX website to display WGS data from the KOLF2.1J cell line. 
URL https://github.com/broadinstitute/hscgp
 
Title Live Cell Quantification using Image Analysis. 
Description We developed pipelines to enable the rapid quantification of cells based on staining by a live-cell non-toxic membrane dye. For applications where there are many conditions in which cells need to be quantified, this approach significantly reduces labor and increases speed, while delivering comparable performance. 
Type Of Material Technology assay or reagent 
Year Produced 2021 
Provided To Others? Yes  
Impact This method allows us to perform a head-to-head comparison of dozens of media conditions in a single experiment, yielding valuable insights into which media conditions best promote genomic stability of stem cells. 
URL https://www.protocols.io/view/live-cell-quantification-using-image-analysis-bzgep3te
 
Title RVG:pff model of PD 
Description We have recently created this novel model of Parkinson's disease in wild-type rats. This is generated by intravenous administration of pathogenic alpha synuclein ifbrils, hich is reversibly complexed with a peptide carrier, and that a single injection through the tail vein is sufficient to generate neurodegeneration and alpha synuclein pathology in the rat brain in a site-specific and dose-dependent way. We have submitted our manuscript to J Clin Invest and is currently revising our paper for resubmission to this journal. 
Type Of Material Model of mechanisms or symptoms - non-mammalian in vivo 
Year Produced 2017 
Provided To Others? No  
Impact Rather than generating transgenic animals or injecting pathogenic substances through intracerebral administration, our one-off, intravenous delivery of foreign substances will have a profound impact on the welfare of animals (3Rs: replacement, reduction and refinement). In addition to the delivery of pathogenic alpha synuclein fibrils, we have also demonstrated the flexibility of our novel strategies by transvascularly delivering a range of other substances including green fluorscent protein and bioactive enzymes. 
 
Title bioinformatic pipeline for analysis of sequencing data from gene-edited cell lines 
Description CRISPR is a powerful way to edit stem cell clones, but identifying cell clones carrying desired edits remains challenging. To address this issue we developed GenEditID, a flexible, open-access platform for sample tracking, analysis and integration of multiplexed deep sequencing and proteomic data, and intuitive plate-based data visualisation to facilitate gene edited clone identification. 
Type Of Material Technology assay or reagent 
Year Produced 2019 
Provided To Others? Yes  
Impact The impact of this work is not immediately clear, but our hope is that it will facilitate other groups and facilities to establish their own high-throughput gene editing workflows. 
URL https://www.biorxiv.org/content/10.1101/657650v1
 
Title Whole-genome sequences of 143 human embryonic stem cell lines that enable rational line selection based on genetic variation 
Description Despite their widespread use in research, there has not yet been a systematic genomic analysis of human embryonic stem cell (hESC) lines at a single-nucleotide resolution. We therefore performed whole-genome sequencing (WGS) of 143 hESC lines and annotated their single-nucleotide and structural genetic variants. We found that while a substantial fraction of hESC lines contained large deleterious structural variants, finer-scale structural and single-nucleotide variants (SNVs) that are ascertainable only through WGS analyses were present in hESC genomes and human blood-derived genomes at similar frequencies. Moreover, WGS allowed us to identify SNVs associated with cancer and other diseases that could alter cellular phenotypes and compromise the safety of hESC-derived cellular products transplanted into humans. As a resource to enable reproducible hESC research and safer translation, we provide a user-friendly WGS data portal and a data-driven scheme for cell line maintenance and selection. 
Type Of Material Database/Collection of data 
Year Produced 2022 
Provided To Others? Yes  
Impact These data have enabled researchers to avoid cell lines that carry genetic abnormalities that would make certain lines less suitable for use, and select those that are best suited based on their genetic characteristics. 
URL https://duos.broadinstitute.org/
 
Description Advanced Bioprocess Services 
Organisation Advanced Bioprocess Services Ltd
Country United Kingdom 
Sector Private 
PI Contribution We have partnered with Advanced Bioprocess Services to deliver technology and process development expertise to clinical stage therapeutic product companies. These have included pre-clinical bioreactor process development and modelling for several Boston (US) based blood products companies, and process development for leading UK based companies in neural stem cell and immunotherapies. Our contribution has been specifically in novel process model development, novel methods to improve process efficiency, and technology design.
Collaborator Contribution Advanced Bioprocess Services manage the interface with companies seeking process development and provide extensive high value reagents and consumables for project work, either directly or via other collaborating companies, as well as providing access to the most relevant and protected industrial processes for development of our research. Since 2016 Advanced Bioprocess Services have directly funded 258,000 GBP of research and impact activity through the University as of end of 2019
Impact Novel industrially applied processes
Start Year 2016
 
Description Astra Zeneca industrial collaboration for universal cell therapies 
Organisation AstraZeneca
Country United Kingdom 
Sector Private 
PI Contribution This is a network based partnership involving several PIs at the Stem Cell Institute, Cambridge, PSEC and Astra Zeneca R&D (based in Gothenburg) with the avowed aim to look at gene editing techniques to product iPSC cell lines from which universal (immune silent) cell therapies can be produced
Collaborator Contribution Exchange of ideas and strategies
Impact Only just started
Start Year 2020
 
Description Austin Smith 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution Epigenomics and multi-omics sequencing
Collaborator Contribution Human and mouse pluripotent stem cells
Impact Several collaborative publications.
Start Year 2013
 
Description Collaboration with Cell Therapy Catapult 
Organisation Cell Therapy Catapult
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Gap analysis for large scale production of platelets in vitro_we are looking to implement them
Collaborator Contribution Gap analysis for large scale production of platelets in vitro_we are looking to implement them
Impact DSTL grant application
Start Year 2020
 
Description Collaboration with Open Targets - NeuroID 
Organisation The Wellcome Trust Sanger Institute
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution We are assisting with the generation of cellular assays, neuronal differentiation, and biological interpretation of resulting data.
Collaborator Contribution Our collaborators are proving expertise in CRISPR gene editing and bioinformatics.
Impact this project has just commenced, so there are no outputs to report at this time
Start Year 2020
 
Description Collaboration with Smart Materials Group (UCL) 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution This is a collaboration looking at the effect if smart materials on the survival and immunogenecity of DA neurons. Our role in the collaboration is to provide the cells, and to provide intellectual input into the study design. This work was initially part of a small grant (mathematical modelling grant from UKRMP), but has now extended beyond the life of that grant.
Collaborator Contribution Our collaborators (James Phillips and team), are experts in biomaterials. They are designing, carrying out an analysing the effects of smart materials on DA cell survival.
Impact Poster presentation
Start Year 2019
 
Description Edited iPSC lines for research on SARS-CoV-2 effect on megakaryocytes and platelets 
Organisation University of Bristol
Country United Kingdom 
Sector Academic/University 
PI Contribution We have generated cell lines knock-out for putative SARS-CoV-2 receptors using the gene editing strategy developed with PSEC
Collaborator Contribution The two Bristol groups (Poole and Davidson) provide experimental support with MKs (Poole) and SARS-CoV-2 co-cultures.
Impact Still ongoing
Start Year 2020
 
Description Jenny Nichols mouse and human embryology 
Organisation University of Cambridge
Country United Kingdom 
Sector Academic/University 
PI Contribution Single cell multi-omics, mutants of epigenetic regulators.
Collaborator Contribution Mouse and human embryos
Impact Several collaborative publications and two joint grants. Multi-disciplinary between epigenetics, multi-omics, embryology, stem cell research.
Start Year 2014
 
Description Lund Collaboration 
Organisation Lund University
Country Sweden 
Sector Academic/University 
PI Contribution Supply of fetal and post mortem brain tissue to collaborators in Lund. Collaboration on the stem cell for parkinson's disease project.
Collaborator Contribution Collaboration on the stem cell for parkinson's disease project.
Impact Publications
Start Year 2010
 
Description Mathematical Modelling Collaboration with UCL 
Organisation University College London
Country United Kingdom 
Sector Academic/University 
PI Contribution This is a brand new collaboration with James Philips and Rebecca Shipley of UCL. We have two collaborative projects which aim to use mathematical modelling approaches to (i) design engineered tissues to improve cell transplantation therapy for Parkinson's disease and (ii) develop novel controlled release biomaterials (eg controlled release immunomodulating agents) for CNS cell therapies. The primary role of the Cambridge research team will be to provide the cellular material, and to perform in vitro immunogenecity assays for the controlled biomaterial project. The collaboration has not yet bought in funds - but we have applied for two UKRMP pump priming grants.
Collaborator Contribution Our UCL partners with provide the mathematical modelling know-how (Rebecca Shipley), and the smart materials expertise.
Impact Nil to date - the collaboration was only formed 1 month ago.
Start Year 2019
 
Description Production of universal platelets from iPSC at GMP 
Organisation NHS National Services Scotland (NSS)
Department Scottish National Blood Transfusion Service
Country United Kingdom 
Sector Public 
PI Contribution Developing an iPSC universal cell line for the production of platelets at GMP
Collaborator Contribution Process development and gene editing at GMP
Impact Process development and gene editing at GMP
Start Year 2020
 
Description UKRMP Collaboration 
Organisation King's College London
Country United Kingdom 
Sector Academic/University 
PI Contribution This award enabled us to form a collaboration with Kings College London and enabled us to apply for and be awarded a UKRMP grant (total award 900K, our portion of the award £328,032). Our research team helped develop the idea behind the grant application, and wrote the application. Within this award/new collaboration we will be utilising our humanised mouse model to test the immunogenecity of ES-DA cells.
Collaborator Contribution Our collaborators also helped develop the idea behind the grant application, and helped to write the application. Within the award/new collaboration they will be testing the immunogenecity of iPSC-hepatocytes in vitro and in vivo (using a humanised mouse model).
Impact Nil yet as this grant/collaboration has only been active a few months.
Start Year 2019
 
Description iNDI collaboration to select hiPSC lines 
Organisation National Institutes of Health (NIH)
Department National Institute of Neurological Disorders and Stroke (NINDS)
Country United States 
Sector Public 
PI Contribution We are assisting with the analysis of whole genome sequencing data, and are differentiating a panel of human induced pluripotent stem cell (hiPSC) lines to various neuronal lineages in order to select a cell line for future use by a consortium.
Collaborator Contribution Our collaborators have selected and obtained a panel of cell lines, have performed whole genome sequencing, and are also differentiating these cell lines down different lineages for comparision.
Impact We are still in the process of analysing data, but plan to meet together in the coming months to select a cell line that will form the basis of large-scale gene editing efforts.
Start Year 2019
 
Title Collaboration agreement 
Description This collaboration agreement covers work to be carried out under the Wellcome Human Developmental Biology Initiative 
IP Reference  
Protection Protection not required
Year Protection Granted 2019
Licensed No
Impact None yet
 
Title Methylome of human blastocysts 
Description Collaboration agreement with Karolinska Institute 
IP Reference  
Protection Protection not required
Year Protection Granted 2017
Licensed No
Impact Several datasets have been obtained
 
Title UKRMP2 pluripotent stem cell and engineered cell hub 
Description Collaboration agreement with PSEC on human pluripotent stem cells 
IP Reference  
Protection Protection not required
Year Protection Granted 2018
Licensed No
Impact Several datasets have been obtained
 
Title RESTORE 
Description Primary haematopoietic progenitors-derived red cells injected into volunteer to show improvement of recovery and survival compared to donor-derived red cells 
Type Therapeutic Intervention - Cellular and gene therapies
Current Stage Of Development Initial development
Year Development Stage Completed 2020
Development Status Under active development/distribution
Clinical Trial? Yes
Impact Inform future large scale production of in vitro derived blood cells 
URL https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2017-002178-38
 
Company Name SAFI BIOSOLUTIONS UK LIMITED 
Description As the cell therapy commercialization partner of a 5-year Department of Defense program to manufacture on-demand blood products, Safi Biosolutions and its collaborators are working to 'crack the code' of Cell Therapy 2.0 challenges of manufacturing at appropriate scale, high consistency of product, and economically viable cost of goods by integrating world-leading expertise in cord blood stem cell expansion, bioprocessing optimization, manufacturing scale-up and cryostorage. Lead development programs for manufactured, on-demand cell therapy products include red blood cells for trauma, tailored red blood cells for specific transfusions (e.g. sickle cell disease) and a neutrophil progenitor cell therapy for the treatment of chemotherapy-induced neutropenia. 
Year Established 2021 
Impact Established an economic manufacturing platform for therapeutic blood products
Website https://safi.bio/
 
Company Name SAFI BIOSOLUTIONS UK LIMITED 
Description As the cell therapy commercialization partner of a 5-year Department of Defense program to manufacture on-demand blood products, Safi Biosolutions and its collaborators are working to 'crack the code' of Cell Therapy 2.0 challenges of manufacturing at appropriate scale, high consistency of product, and economically viable cost of goods by integrating world-leading expertise in cord blood stem cell expansion, bioprocessing optimization, manufacturing scale-up and cryostorage. Lead development programs for manufactured, on-demand cell therapy products include red blood cells for trauma, tailored red blood cells for specific transfusions (e.g. sickle cell disease) and a neutrophil progenitor cell therapy for the treatment of chemotherapy-induced neutropenia. 
Year Established 2021 
Impact Established an economic manufacturing platform for therapeutic blood products
Website https://safi.bio/
 
Company Name SAFI BIOSOLUTIONS UK LIMITED 
Description As the cell therapy commercialization partner of a 5-year Department of Defense program to manufacture on-demand blood products, Safi Biosolutions and its collaborators are working to 'crack the code' of Cell Therapy 2.0 challenges of manufacturing at appropriate scale, high consistency of product, and economically viable cost of goods by integrating world-leading expertise in cord blood stem cell expansion, bioprocessing optimization, manufacturing scale-up and cryostorage. Lead development programs for manufactured, on-demand cell therapy products include red blood cells for trauma, tailored red blood cells for specific transfusions (e.g. sickle cell disease) and a neutrophil progenitor cell therapy for the treatment of chemotherapy-induced neutropenia. 
Year Established 2021 
Impact Established an economic manufacturing platform for therapeutic blood products
Website https://safi.bio/
 
Company Name SAFI BIOSOLUTIONS UK LIMITED 
Description As the cell therapy commercialization partner of a 5-year Department of Defense program to manufacture on-demand blood products, Safi Biosolutions and its collaborators are working to 'crack the code' of Cell Therapy 2.0 challenges of manufacturing at appropriate scale, high consistency of product, and economically viable cost of goods by integrating world-leading expertise in cord blood stem cell expansion, bioprocessing optimization, manufacturing scale-up and cryostorage. Lead development programs for manufactured, on-demand cell therapy products include red blood cells for trauma, tailored red blood cells for specific transfusions (e.g. sickle cell disease) and a neutrophil progenitor cell therapy for the treatment of chemotherapy-induced neutropenia. 
Year Established 2021 
Impact Established an economic manufacturing platform for therapeutic blood products
Website https://safi.bio/
 
Company Name ADVANCED BIOPROCESS SERVICES LIMITED 
Description Bioprocess Development Service Provider for Cell and Gene Therapies 
Year Established 2016 
Impact Worked with a range of early stage cell and gene therapy companies to deliver novel, economic, and robust manufacturing processes for pre-clinical models; provided the development services that have directly supported in excess of $20M of private raise.
 
Company Name ADVANCED BIOPROCESS SERVICES LIMITED 
Description Bioprocess Development Service Provider for Cell and Gene Therapies 
Year Established 2016 
Impact Worked with a range of early stage cell and gene therapy companies to deliver novel, economic, and robust manufacturing processes for pre-clinical models; provided the development services that have directly supported in excess of $20M of private raise.
 
Company Name ADVANCED BIOPROCESS SERVICES LIMITED 
Description Bioprocess Development Service Provider for Cell and Gene Therapies 
Year Established 2016 
Impact Worked with a range of early stage cell and gene therapy companies to deliver novel, economic, and robust manufacturing processes for pre-clinical models; provided the development services that have directly supported in excess of $20M of private raise.
 
Company Name CELLADVICE LTD 
Description Consultancy company specialising in blood transfusion and cell therapies 
Year Established 2019 
Impact Currently providing expert advice to 4 different companies
 
Company Name XAP THERAPEUTICS LIMITED 
Description Start up looking to make new therapeutics based on platelets produced in vitro 
Year Established 2017 
Impact None as yet
 
Company Name XAP THERAPEUTICS LIMITED 
Description Start up looking to make new therapeutics based on platelets produced in vitro 
Year Established 2017 
Impact None as yet
 
Company Name XAP THERAPEUTICS LIMITED 
Description Start up looking to make new therapeutics based on platelets produced in vitro 
Year Established 2017 
Impact None as yet
 
Description Webinar & Q&A Session - WHAT HAS CHANGED IN PARKINSON'S SINCE MY LAST TALK IN 2012? A PERSONAL PERSPECTIVE 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact Live webinar and Q&A session for patients, families and clinicians for Edinburgh PUK branch annual lecture
Year(s) Of Engagement Activity 2021
 
Description BSGCT AGM - Plenary Lecture 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact Invited speaker to discuss development of cell transplantation for Parkinson's disease
Year(s) Of Engagement Activity 2019
 
Description British Neurosurgery Trainee Meeting, Robinson College, Cambridge 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact A talk entitled: Disorders of the motor system and the current and future treatment of Parkinson's disease
Year(s) Of Engagement Activity 2020
 
Description Cambridge Science Festival 2020 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact A stall from the IMS at the Cambridge Science Festival educated the general public about issues in obesity and metabolic science
Year(s) Of Engagement Activity 2020
 
Description Cell Symposia: Translation of Stem Cells to the Clinic 2018 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited talk on stem cell therapies for PD
Year(s) Of Engagement Activity 2018
 
Description Charity Concert All Saints 2018 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Charity concert at which I and professional musicians performed as well as children of the local drama school. The concept was supported by the Cambridge Stem Cell Institute and the benefits went to Naitbabies.org, a patient organisation supporting patients affected by neonatal alloimmune thrombocytopenia
Year(s) Of Engagement Activity 2018
 
Description Charity concert 2019 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Charity concert in Newmarket for the benefit of the East Anglia Air Ambulance_PhD students and post-doc presented some of their stem cell work in the context of regenerative medicine to the general public who attended the concert
Year(s) Of Engagement Activity 2019
 
Description Clinical Neuroscience - Departmental Away Day 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Professional Practitioners
Results and Impact A debate entitled - The great debate - stem cells for brain diseases: the only hope of a cure
Year(s) Of Engagement Activity 2019
 
Description Departmental seminar, Edinburgh 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Professional Practitioners
Results and Impact A talk presented at Edinburgh departmental neurology meeting: How disease stratification impacts on the experimental therapeutic landscape in PD
Year(s) Of Engagement Activity 2018
 
Description G Force PD 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact G FORCE PD is an international collaboration between members of various academic institutes to discuss the process of taking stem cell therapies to clinic in patients with Parkinon's disease
Year(s) Of Engagement Activity 2018
 
Description G Force PD 2019 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A talk given at the annual G Force PD meeting and a follow up public lecture on Parkinson's disease and stem cell therapies.
Year(s) Of Engagement Activity 2019
 
Description Generation of video to highlight the role of minorities in science 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact A graduate student in my group generated a video with the assistance of the University of Cambridge to raise awareness of the impact of minority researchers. This video has been posted to YouTube and has been viewed more than 1800 times.
Year(s) Of Engagement Activity 2018
URL https://www.youtube.com/watch?v=f90C-psTPkk&t=21s
 
Description Genome editing workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Workshop about Crispr genome editing at the Cambridge Science Festival
Year(s) Of Engagement Activity 2019
 
Description How close are we to delivering a stem cell based therapy in Parkinson's Disease 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Recorded plenary lecture as part of Korean Stem Cell Society AGM
Year(s) Of Engagement Activity 2021
 
Description ISSCR - LA - Inductry session 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Talk entitled, developing an investigational IND for Parkinson's disease
Year(s) Of Engagement Activity 2019
 
Description ISSCR, Melbourne 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact Invited speaker at the International society for stem cell research, held in Melbourne, Australia. Roger gave 3 talks during the whole event.
Year(s) Of Engagement Activity 2018
 
Description Invited Speaker - ISSCR Meeting on Ethics 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Discussion around the ethical challenges of taking stem cells to clinical therapy
Year(s) Of Engagement Activity 2019
 
Description Invited Speaker - Miltenyi GMBH 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact A talk given entitled, From clinic to bench to clinic - the basis of the heterogeneity of PD and its therapeutic implications
Year(s) Of Engagement Activity 2019
 
Description Invited Speaker - NECTAR 2019 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A talk on Transeuro - Lessons Learned
Year(s) Of Engagement Activity 2019
 
Description Invited Speaker- Novo Nordisk, Copenhagen 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Industry/Business
Results and Impact A discussion around stem cell therapies for Parkinson's disease
Year(s) Of Engagement Activity 2019
 
Description Lessons learnt from TransEuro for taking a cell based therapy to clinic 
Form Of Engagement Activity A broadcast e.g. TV/radio/film/podcast (other than news/press)
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact EU Networking meeting to discuss the lessons learnt from TransEuro for taking a cell based therapy to clinic, web-based seminar.
Year(s) Of Engagement Activity 2019,2020
 
Description Lichfield - Science and Engineering Society 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Public/other audiences
Results and Impact Can we repair the chronically degenerating brain?
Year(s) Of Engagement Activity 2019
 
Description Live Webinar - DOPAMINE CELL THERAPIES FOR PARKINSON'S DISEASE- WHY BOTHER? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Annual general meeting of NCER consortium, Luxembourg
Year(s) Of Engagement Activity 2021
 
Description Live Webinar - THE NON DOPAMINERGIC ASPECTS OF PARKINSON'S DISEASE- HOW CAN STEM CELL THERAPIES SPEAK TO THEM? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Third sector organisations
Results and Impact Live Webinar as part of the NSC-Recontruct workshop in Rome
Year(s) Of Engagement Activity 2021
 
Description Live talk - TransEuro- lessons learnt to date 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Live (in person) talk at the NECTAR meeting - 16th International Symposium on Neural Transplantation and Repair (INTR) and 31st ECTAR meeting, Edinburgh.
Year(s) Of Engagement Activity 2021
 
Description Live webinar - CAN WE REPAIR THE AGING DEGENERATING HUMAN BRAIN? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact Live webinar for CUH BRC PPIE group
Year(s) Of Engagement Activity 2021
 
Description Masters in Therapeutics Science students 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact A talk on, Can we repair the chronically degenerating brain?
Year(s) Of Engagement Activity 2020
 
Description Oxford Stem Cell Institute annual meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Postgraduate students
Results and Impact An invited talk on Stem Cells and Parkinson's disease - where are we therapeutically to students and scientists
Year(s) Of Engagement Activity 2018
 
Description Parkinson's Disease Open Day 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Patients, carers and/or patient groups
Results and Impact Annual Parkinson's disease open day held at the John Van Geest Centre for Brain Repair, patients and carers are invited to attend and the ongoing research of the Barker Lab is presented.
Year(s) Of Engagement Activity 2019
 
Description Participant in Roundtable discussion hosted by Nature magazine 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Other audiences
Results and Impact A round-table discussion in front of an audience of over 100 professors, postdocs, editors, and policy makers debated the issues surrounding the safety and genetic stability of human stem cell-based research. The results will be published and disseminated via the web to reach a much larger audience.
Year(s) Of Engagement Activity 2018
 
Description Participant in public meeting hosted by ThermoFisher 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact A public discussion of issues relating to stem cell genomic stability helped to inform issues relevant to stem cell basic and translation research.
Year(s) Of Engagement Activity 2018
 
Description Public Engagement Champion Cambridge Stem Cell Institute 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Public/other audiences
Results and Impact I have been nominated as the Public Engagement Champion of the CSCI_in short I am the academic PI supporting the Public Engagement team including chairing regular meetings and shaping strategy and implementation thereof
Year(s) Of Engagement Activity 2019,2020
 
Description Stem Cell Symposium 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Other audiences
Results and Impact This debate was for scientists
Year(s) Of Engagement Activity 2018
 
Description TAKING A DOPAMINE STEM CELL THERAPY TO PATIENTS WITH PARKINSON'S DISEASE- LESSONS LEARNT (SO FAR!) 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact IT WAS A TALK DESCRIBING THE CHALLENGES OF TAKING A STEM CELL PRODUCT TO A FIRST IN HUMAN TRIAL.
Year(s) Of Engagement Activity 2020
 
Description THE CHALLENGES OF TAKING A DOPAMINE CELL BASED THERAPY TO PATIENTS WITH PARKINSON'S DISEASE- IS IT WORTH IT? 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Recorded as part of a Nova programme of talks for MDS meeting delivered to Neurologists
Year(s) Of Engagement Activity 2021
 
Description Webinar - Cell therapies for Parkinson's Disease 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact Webinar to engage and inform university students
Year(s) Of Engagement Activity 2021
 
Description Webinar - HOW CAN ONE BEST TEST A STEM CELL BASED DOPAMINE THERAPY FOR PATIENTS WITH PARKINSON'S DISEASE? 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Webinar for the German Stem Cell network- 10th International meeting
Year(s) Of Engagement Activity 2021
 
Description Webinar - THE CHALLENGES OF TAKING A DOPAMINE CELL BASED THERAPY TO PATIENTS WITH PARKINSON'S DISEASE- IS IT WORTH IT? 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Professional Practitioners
Results and Impact Invited lecturer to deliver the annual Druker lecture at Harvard Medical School
Year(s) Of Engagement Activity 2021
 
Description Weert College ethics workshop 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Schools
Results and Impact This was a scientific ethics workshop for a school in the Netherlands
Year(s) Of Engagement Activity 2019
 
Description development of a Neurodegeneration Community Building initiative 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach Regional
Primary Audience Professional Practitioners
Results and Impact We have developed a community building initiative to bring together groups in Cambridge working in neurodegeneration. We have held smaller events focused on researchers, but are planning a symposium for May or June that will involve patients and patient advocates.
Year(s) Of Engagement Activity 2020
 
Description hosted student in the laboratory 
Form Of Engagement Activity Participation in an open day or visit at my research institution
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Undergraduate students
Results and Impact We hosted an undergraduate student in the laboratory for 2 days. She had an interest in biology and sought to gain insight into a career in science. Since visiting the lab, she has applied to MPhil and PhD programmes.
Year(s) Of Engagement Activity 2019
 
Description presentation to a primary school 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Geographic Reach Local
Primary Audience Schools
Results and Impact I gave a talk about the brain and the neuroscience of appetite regulation at a local primary school to all grade levels (approximately 210 students). This sparked over 1 hour of questions and the school reported increased interest in the brain and many questions in class in this area.
Year(s) Of Engagement Activity 2019