Chondrocytes from Clinical Grade Embryonic Stem Cells
Lead Research Organisation:
University of Manchester
Department Name: School of Biological Sciences
Abstract
Osteoarthritis is a debilitating condition of joints affecting 25% of adults over 65 yrs (WHO estimate). It causes pain, disability and loss of independence, which results in a poor quality of life. In the EU it is ranked 12th for disease burden with 35-40 million sufferers and this is set to rise with increased ageing of the population. Current clinical treatment is limited to pain relief with nothing able to delay or reverse the condition. Irreversibly damaged joints are eventually replaced by synthetic prostheses, which are successful in older patients (>65), but less so in younger patients whose life expectancy is much greater than that of the prosthesis and revision surgery is less successful. There is therefore a large unmet clinical need for improved treatment for OA. Current strategies include cartilage repair (ACI) using the patient's own chondrocytes, harvested from intact areas of tissue. However, the outcome of ACI is little better than non-cellular orthopaedic treatments and it requires 2 operations and damage to otherwise intact tissue. Patients' stem cells are also being tested from bone marrow, but this also requires 2 operations and patient specific cell culture. To overcome the problem of the variable quality of the patients' own cells and the need for 2 operations, we have developed a protocol to generate chondrocytes from human embryonic stem cells (hESCs). The protocol is entirely serum free, chemically defined and yields up to 97% chondrogenic cells. We now need to adapt this procedure to deliver cells suitable for clinical applications. This requires the use of entirely validated clinical grade reagents, scale up to generate larger numbers of cells and methods to store and deliver cells to the clinic. We will validate this protocol with a new generation of very high quality (clinical grade) stem cell lines derived in Manchester and by other Centres across the UK. The advantage of using hESCs is that they can be expanded to produce enough chondrogenic cells to treat large numbers of patients, making such a therapy cost-effective on the NHS. Follow-up tests in vivo will grade lines for success in repairing focal defects in rat knee joints (already shown for research grade cells) to allow us to assess the quality of in vivo cartilage repair and assess any incidence of tumour formation, or other adverse effects. The plan will show if hESC derived chondrocytes can be produced, delivered and are able to complete hyaline cartilage repair. This award will allow us to establish the means and methods to move forward towards phase 1 clinical trials for patients with focal cartilage defects.
Technical Summary
Current clinical treatment for osteoarthritis, which affects 25% of adults over 65 yrs (WHO estimate), is limited to pain relief and there is no treatment able to delay or reverse the condition. Irreversibly damaged joints are eventually replaced by synthetic prostheses, which are successful in older patients (>65), but less so in younger patients whose life expectancy is much greater than that of the prosthesis and revision surgery is less successful. There is therefore a large unmet clinical need for improved treatment for OA. To address this need we developed a protocol to differentiate pluripotent stem cells to chondrogenic cells at high efficiency and these cells which can repair cartilage defects in a rodent model. The protocol is entirely serum free, chemically defined and yields up to 97% chondrogenic cells. We will now adapt this procedure to deliver cells suitable for clinical applications, meeting current Good Manufacturing Practice (cGMP ) standards. We will employ strategies leading to greater cell expansion; apply our refined protocol to a range of clinical grade hESC lines derived in Manchester and in other Centres, evaluating lines for chondrogenic bias. The differentiated cells will be tested for their ability to repair a surgical cartilage defect, without evidence of adverse effects including the generation of ectopic growths or tumours in i) a rat defect model and ii) in a pilot study for a larger animal, the sheep. We will develop and test methods for the clinical delivery and storage of the cells using fibrin gels, evaluating viability and shelf life.
Planned Impact
We intend this preclinical application to lead to the development of phase 1 clinical trials which will provide direct patient benefit and new treatment options for joint trauma and OA sufferers. This will be for focal cartilage defects in the first instance but with potential for repairing larger OA lesions as clinical experience is gained. We will generate hESC-chondrocytes which are suitable for use for patients as part of planning for subsequent clinical trials with our clinical collaborators (Sanjay Anand and David Johnson, Stockport NHS Trust). The development of our protocol will lead the way in providing proof of principle for cell therapies from pluripotent cells for both academics and clinicians.
Academics will benefit from our development and refinement of reproducible protocols, increased understanding of cartilage development and homeostasis. Our work will provide in vitro and in vivo model system for understanding responses to inflammatory mediators and extracellular matrix targeted drugs. We will interact with members of the UK Regenerative Medicine platform hubs to share our findings of translation and learn from their experiences, exploiting their findings where possible e.g. in imaging and safety.
NHS: Our work will start to open up a pathway for this and similar therapies to be incorporated into NHS treatments.
Regulators: Our engagement with the regulators will also help to inform regulatory procedures for cell therapy especially those from pluripotent cells.
Patient Groups and General public: Firstly our projected therapy will provide a cell based treatment and so make a real impact on the quality of life to patients with sports injury and osteoarthritis. Secondly, we will engage with patient groups and member of the public to inform them of our activities and learn further from them regarding patient perception of need, in a continuation of our previous public engagement activities.
Biopharma: We will interact further with companies interested in cell therapy or who may wish to use our findings to generate new in vitro models for testing drugs active in modulating extracellular matrix repair. We will seek advice from biopharma and the Catapult with a view to their active engagement as we move towards the clinic.
Academics will benefit from our development and refinement of reproducible protocols, increased understanding of cartilage development and homeostasis. Our work will provide in vitro and in vivo model system for understanding responses to inflammatory mediators and extracellular matrix targeted drugs. We will interact with members of the UK Regenerative Medicine platform hubs to share our findings of translation and learn from their experiences, exploiting their findings where possible e.g. in imaging and safety.
NHS: Our work will start to open up a pathway for this and similar therapies to be incorporated into NHS treatments.
Regulators: Our engagement with the regulators will also help to inform regulatory procedures for cell therapy especially those from pluripotent cells.
Patient Groups and General public: Firstly our projected therapy will provide a cell based treatment and so make a real impact on the quality of life to patients with sports injury and osteoarthritis. Secondly, we will engage with patient groups and member of the public to inform them of our activities and learn further from them regarding patient perception of need, in a continuation of our previous public engagement activities.
Biopharma: We will interact further with companies interested in cell therapy or who may wish to use our findings to generate new in vitro models for testing drugs active in modulating extracellular matrix repair. We will seek advice from biopharma and the Catapult with a view to their active engagement as we move towards the clinic.
Publications
Mancini FE
(2024)
Effect of a retinoic acid analogue on BMP-driven pluripotent stem cell chondrogenesis.
in Scientific reports
Humphreys PEA
(2023)
Optogenetic manipulation of BMP signaling to drive chondrogenic differentiation of hPSCs.
in Cell reports
Morais MRPT
(2022)
Kidney organoids recapitulate human basement membrane assembly in health and disease.
in eLife
Luo L
(2022)
Hydrostatic pressure promotes chondrogenic differentiation and microvesicle release from human embryonic and bone marrow stem cells.
in Biotechnology journal
Smith CA
(2022)
SIRT1 activity orchestrates ECM expression during hESC-chondrogenic differentiation.
in FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Ferreira MJS
(2022)
Pluripotent stem cells for skeletal tissue engineering.
in Critical reviews in biotechnology
Naven MA
(2022)
Development of human cartilage circadian rhythm in a stem cell-chondrogenesis model.
in Theranostics
Cain SA
(2022)
ADAMTS6 cleaves the large latent TGFß complex and increases the mechanotension of cells to activate TGFß.
in Matrix biology : journal of the International Society for Matrix Biology
Aboussahoud WS
(2021)
The expression and activity of Toll-like receptors in the preimplantation human embryo suggest a new role for innate immunity.
in Human reproduction (Oxford, England)
Humphreys PA
(2020)
Optogenetic Control of the BMP Signaling Pathway.
in ACS synthetic biology
Moxon SR
(2020)
A Preliminary Evaluation of the Pro-Chondrogenic Potential of 3D-Bioprinted Poly(ester Urea) Scaffolds.
in Polymers
Fonseca AC
(2020)
Emulating Human Tissues and Organs: A Bioprinting Perspective Toward Personalized Medicine.
in Chemical reviews
Griffiths R
(2020)
The Transcription Factor-microRNA Regulatory Network during hESC-chondrogenesis.
in Scientific reports
Smith HL
(2019)
Systems based analysis of human embryos and gene networks involved in cell lineage allocation.
in BMC genomics
Wang T
(2019)
Enhanced chondrogenesis from human embryonic stem cells.
in Stem cell research
Cheng A
(2018)
Recombinant Extracellular Matrix Protein Fragments Support Human Embryonic Stem Cell Chondrogenesis.
in Tissue engineering. Part A
Ye J
(2017)
High quality clinical grade human embryonic stem cell lines derived from fresh discarded embryos.
in Stem cell research & therapy
Vitillo L
(2017)
Integrin and FAK Regulation of Human Pluripotent Stem Cells.
in Current stem cell reports
Sunde A
(2016)
Time to take human embryo culture seriously.
in Human reproduction (Oxford, England)
Leese HJ
(2016)
Biological optimization, the Goldilocks principle, and how much is lagom in the preimplantation embryo.
in Molecular reproduction and development
Wilkinson J
(2016)
No common denominator: a review of outcome measures in IVF RCTs.
in Human reproduction (Oxford, England)
Vitillo L
(2016)
Integrin-Associated Focal Adhesion Kinase Protects Human Embryonic Stem Cells from Apoptosis, Detachment, and Differentiation.
in Stem cell reports
Canham MA
(2015)
The Molecular Karyotype of 25 Clinical-Grade Human Embryonic Stem Cell Lines.
in Scientific reports
Villarin BL
(2015)
Polymer Supported Directed Differentiation Reveals a Unique Gene Signature Predicting Stable Hepatocyte Performance.
in Advanced healthcare materials
Cheng A
(2014)
Cartilage repair using human embryonic stem cell-derived chondroprogenitors.
in Stem cells translational medicine
Bolton VN
(2014)
ACE consensus meeting report: culture systems.
in Human fertility (Cambridge, England)
Harper JC
(2014)
Current evidence for ART practice: the Cochrane of Cochranes on optimising outcomes.
in Evidence-based medicine
Cheng A
(2014)
Generating cartilage repair from pluripotent stem cells.
in Tissue engineering. Part B, Reviews
Brison DR
(2014)
Metabolic heterogeneity during preimplantation development: the missing link?
in Human reproduction update
Title | Additional file 2: of Systems based analysis of human embryos and gene networks involved in cell lineage allocation |
Description | Figure S1. Un-normalised Affymetrix microarrays A) Boxplots represent summaries of the signal intensity distributions of the arrays. Each box corresponds to one array. B) Boxplot outlier detection was performed by computing the Kolmogorov-Smirnov statistic Kabetween each array's distribution and the distribution of the pooled data. None of the samples have medians higher than 1.05, which would represent a low quality array C) Density distributions of the log2intensities grouped by the matching type of the probes. The blue line shows a density estimate (smoothed histogram) from intensities of perfect match probes (PM), the grey line, one from the mismatch probes (MM). D) RNA digestion plot. The shown values are computed from the pre-processed data. Each array is represented by a single line. E) MA plots (M = log2 (I1)-log2 (I2), A = 1/2(log2 (I1) + log2 (I2)), where I1 is the intensity of the array studied, and I2 is the intensity of a "pseudo"-array that consists of the median across arrays. The mass of the distribution in an MA plot should be concentrated along the M = 0 axis, and there should be no trend in M as a function of A. Shown are first the 4 arrays with the highest values of Da, then the 4 arrays with the lowest values. F) An example of feature intensities representing the arrays' spatial distributions (M). Figure S2. A and B) Embryonic genome activation (EGA) interaction networks, differential regulation within the 8-cell and blastocyst compared to the 4-cell. C and D) Metanodes of the 8-cell and blastocyst compared to the 4-cell, metanodes as defined by the Cytoscape plugin 'Moduland', metanodes represent genes most central within each module. Red genes represent up-regulation, green nodes represent down-regulation and pink nodes represent non-differentially regulated genes but baseline expressed direct interaction partners. E and F) Tables of network module members. Metanodes represent the most centrally connected gene within a module alongside the next 10 centrally connected genes within each module. Modules are ranked in order from most to least centrally connected within the specific developmental network. Yellow highlighted genes are also identified as Ingenuity causal network genes. Figure S3. A) TRIM28 upstream regulatory network in blastocysts. MDM2 is the only target gene regulated by both upstream regulators MYC and TP53. TRIM28 together with MYC and TP53, may represent the upstream transcriptional control network over the MDM2 module in the blastocyst and provide upstream regulation of epigenetic networks. B) MDM2 is identified as a key module and upstream regulator at the blastocyst stage. MDM2 together with 22 participating regulators, controls the expression of 93 differentially regulated genes within the blastocyst. The participating regulator, transcription factor GATA3, is up-regulated 867-fold in the blastocyst. Pink nodes represent genes identified within module analysis and red nodes represent genes identified within both module and upstream regulatory network analysis. Pathway analysis of the MDM2 module reveals statistically over-represented (p = 0.05) Reactome pathways, ordered from 1 to 10 according to their significance p-value. The MDM2 module is biologically relevant, with 6/10 of the top MDM2 module genes being members of the hedgehog signalling 'on state' pathway. Figure S4. A) 107 co-expression functional modules B) The frequency a module of a specific size was detected using co-expression analysis. C) Overlap of the intra-modular hubs between different methods. In order to have enough genes for the comparison between different methods, all the co-expression modules for the robustness evaluation were selected by including more than 5 genes. The diagonal of the table indicates the numbers of the total genes in each method; the lower triangular matrix shows the numbers of overlapping genes between the corresponding two methods; the upper triangular matrix shows the hypergeometric p-values for the numbers of overlapping genes. Figure S5. Each panel represents a single 8-cell blastomeres top 25 network modules (columns) and the top 10 centrally connected genes within each module. Blastomere networks and modules identified using the absolute expression values of 8-cell blastomeres. Modules are ranked in order from most (left) to least (right) centrally connected within the specific blastomere network. The most centrally connected gene within each module are shown in bold and the remaining genes are ranked from most (top) to least (bottom) centrally connected within a specific module. Blue highlighted genes are also identified as upstream regulatory genes. Figure S6. qPCR expression (?Ct) of Hippo signalling, pluripotency and polarity genes across three sets of 8-cell blastomeres. The first set of blastomers are labelled A1-A8, the second set of blastomeres are labelled B1-B8 and the final set of blastomeres are labelled C1-C8. ?Ct was calculated as 40-Ct. Positive and negative bars represent standard error of the mean. Figure S7. Heat map of individual 8-cell blastomere RNAseq data extracted from Petropoulos et al. Heatmap displays individual 8-cell blastomeres on the horizontal axis and genes on the vertical axis. Individual blastomeres are clustered according to gene expression similarity. After outlier removal we used 59 of the 81 published samples. Embryo origin normalised and variance filter applied (0.21) to exclude noise. Resulting in 588 probes, separated into four groups based on hierarchal clustering. Red represents increased gene expression and blue represents decreased gene expression. (PPTX 6500 kb) |
Type Of Art | Film/Video/Animation |
Year Produced | 2019 |
URL | https://springernature.figshare.com/articles/Additional_file_2_of_Systems_based_analysis_of_human_em... |
Title | Additional file 2: of Systems based analysis of human embryos and gene networks involved in cell lineage allocation |
Description | Figure S1. Un-normalised Affymetrix microarrays A) Boxplots represent summaries of the signal intensity distributions of the arrays. Each box corresponds to one array. B) Boxplot outlier detection was performed by computing the Kolmogorov-Smirnov statistic Kabetween each array's distribution and the distribution of the pooled data. None of the samples have medians higher than 1.05, which would represent a low quality array C) Density distributions of the log2intensities grouped by the matching type of the probes. The blue line shows a density estimate (smoothed histogram) from intensities of perfect match probes (PM), the grey line, one from the mismatch probes (MM). D) RNA digestion plot. The shown values are computed from the pre-processed data. Each array is represented by a single line. E) MA plots (M = log2 (I1)-log2 (I2), A = 1/2(log2 (I1) + log2 (I2)), where I1 is the intensity of the array studied, and I2 is the intensity of a "pseudo"-array that consists of the median across arrays. The mass of the distribution in an MA plot should be concentrated along the M = 0 axis, and there should be no trend in M as a function of A. Shown are first the 4 arrays with the highest values of Da, then the 4 arrays with the lowest values. F) An example of feature intensities representing the arrays' spatial distributions (M). Figure S2. A and B) Embryonic genome activation (EGA) interaction networks, differential regulation within the 8-cell and blastocyst compared to the 4-cell. C and D) Metanodes of the 8-cell and blastocyst compared to the 4-cell, metanodes as defined by the Cytoscape plugin 'Moduland', metanodes represent genes most central within each module. Red genes represent up-regulation, green nodes represent down-regulation and pink nodes represent non-differentially regulated genes but baseline expressed direct interaction partners. E and F) Tables of network module members. Metanodes represent the most centrally connected gene within a module alongside the next 10 centrally connected genes within each module. Modules are ranked in order from most to least centrally connected within the specific developmental network. Yellow highlighted genes are also identified as Ingenuity causal network genes. Figure S3. A) TRIM28 upstream regulatory network in blastocysts. MDM2 is the only target gene regulated by both upstream regulators MYC and TP53. TRIM28 together with MYC and TP53, may represent the upstream transcriptional control network over the MDM2 module in the blastocyst and provide upstream regulation of epigenetic networks. B) MDM2 is identified as a key module and upstream regulator at the blastocyst stage. MDM2 together with 22 participating regulators, controls the expression of 93 differentially regulated genes within the blastocyst. The participating regulator, transcription factor GATA3, is up-regulated 867-fold in the blastocyst. Pink nodes represent genes identified within module analysis and red nodes represent genes identified within both module and upstream regulatory network analysis. Pathway analysis of the MDM2 module reveals statistically over-represented (p = 0.05) Reactome pathways, ordered from 1 to 10 according to their significance p-value. The MDM2 module is biologically relevant, with 6/10 of the top MDM2 module genes being members of the hedgehog signalling 'on state' pathway. Figure S4. A) 107 co-expression functional modules B) The frequency a module of a specific size was detected using co-expression analysis. C) Overlap of the intra-modular hubs between different methods. In order to have enough genes for the comparison between different methods, all the co-expression modules for the robustness evaluation were selected by including more than 5 genes. The diagonal of the table indicates the numbers of the total genes in each method; the lower triangular matrix shows the numbers of overlapping genes between the corresponding two methods; the upper triangular matrix shows the hypergeometric p-values for the numbers of overlapping genes. Figure S5. Each panel represents a single 8-cell blastomeres top 25 network modules (columns) and the top 10 centrally connected genes within each module. Blastomere networks and modules identified using the absolute expression values of 8-cell blastomeres. Modules are ranked in order from most (left) to least (right) centrally connected within the specific blastomere network. The most centrally connected gene within each module are shown in bold and the remaining genes are ranked from most (top) to least (bottom) centrally connected within a specific module. Blue highlighted genes are also identified as upstream regulatory genes. Figure S6. qPCR expression (?Ct) of Hippo signalling, pluripotency and polarity genes across three sets of 8-cell blastomeres. The first set of blastomers are labelled A1-A8, the second set of blastomeres are labelled B1-B8 and the final set of blastomeres are labelled C1-C8. ?Ct was calculated as 40-Ct. Positive and negative bars represent standard error of the mean. Figure S7. Heat map of individual 8-cell blastomere RNAseq data extracted from Petropoulos et al. Heatmap displays individual 8-cell blastomeres on the horizontal axis and genes on the vertical axis. Individual blastomeres are clustered according to gene expression similarity. After outlier removal we used 59 of the 81 published samples. Embryo origin normalised and variance filter applied (0.21) to exclude noise. Resulting in 588 probes, separated into four groups based on hierarchal clustering. Red represents increased gene expression and blue represents decreased gene expression. (PPTX 6500 kb) |
Type Of Art | Film/Video/Animation |
Year Produced | 2019 |
URL | https://springernature.figshare.com/articles/Additional_file_2_of_Systems_based_analysis_of_human_em... |
Description | Cochrane guideline on embryo culture temperature |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
Description | ESHRE working group on the impact of embryo culture medium on long term health |
Geographic Reach | Europe |
Policy Influence Type | Influenced training of practitioners or researchers |
Description | Influencing policy towards patenting of discoveries using hESC lines |
Geographic Reach | Europe |
Policy Influence Type | Membership of a guideline committee |
Description | National Clinical human Embryonic Stem Cell Forum |
Geographic Reach | National |
Policy Influence Type | Membership of a guideline committee |
Impact | Standardisation of requirements for clinical grade embryonic stem cell lines. Prof Brison is vice-chair of this group |
Description | Setting standards for procurement of embryonic stem cells at clinical grade |
Geographic Reach | National |
Policy Influence Type | Influenced training of practitioners or researchers |
Description | 21EBTA Driving Pluripotent Stem Cell Osteogenesis with Light for Tissue Engineering |
Amount | £355,915 (GBP) |
Funding ID | BB/W013940/1 |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 02/2022 |
End | 01/2024 |
Description | TCES Travel awards |
Amount | £300 (GBP) |
Organisation | Tissue and Cell Engineering Society |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 03/2019 |
End | 04/2019 |
Description | Understanding Acrodysostosis type 1 and 2 through a pluripotent stem cell-disease model. |
Amount | £720,311 (GBP) |
Funding ID | MR/X002020/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 09/2022 |
End | 03/2026 |
Description | Understanding an endogenous mechanism that protects against osteoarthritis; towards a new paradigm for disease management |
Amount | £1,315,313 (GBP) |
Funding ID | 22277 |
Organisation | Versus Arthritis |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 01/2020 |
End | 04/2024 |
Title | Constructs for light driven differention |
Description | Light driven BMPR1a and 1b constructs for driving human stem cell development |
Type Of Material | Technology assay or reagent |
Year Produced | 2024 |
Provided To Others? | Yes |
Impact | Too early |
Title | GFP labelled human ESCs |
Description | Human ESCs were labelled with GFP using lentiviral vector. |
Type Of Material | Cell line |
Provided To Others? | No |
Impact | These cells could be used for studies requiring tracing cell migration or destination. |
Title | Repair of cartilage defect in sheep |
Description | Development of method to repair osteochondral defect in a large animal |
Type Of Material | Physiological assessment or outcome measure |
Provided To Others? | No |
Impact | No impact yet but paper will be written shortly |
Title | immortalisation of GMP grade fibroblasts under clean room conditions |
Description | immortalisation of GMP grade fibroblasts under clean room conditions |
Type Of Material | Cell line |
Year Produced | 2013 |
Provided To Others? | Yes |
Impact | Research advance and help to UKSCB |
Title | Additional file 1: of High quality clinical grade human embryonic stem cell lines derived from fresh discarded embryos |
Description | Supplemental information includes supplemental experimental procedures, one figure and one table. (ZIP 292 kb) |
Type Of Material | Database/Collection of data |
Year Produced | 2017 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_1_of_High_quality_clinical_grad... |
Title | Additional file 1: of High quality clinical grade human embryonic stem cell lines derived from fresh discarded embryos |
Description | Supplemental information includes supplemental experimental procedures, one figure and one table. (ZIP 292 kb) |
Type Of Material | Database/Collection of data |
Year Produced | 2017 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/dataset/Additional_file_1_of_High_quality_clinical_grad... |
Title | Additional file 3: of Systems based analysis of human embryos and gene networks involved in cell lineage allocation |
Description | Supplemental Tables (XLSX 274 kb) |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_3_of_Systems_based_analysis_of_human_em... |
Title | Additional file 3: of Systems based analysis of human embryos and gene networks involved in cell lineage allocation |
Description | Supplemental Tables (XLSX 274 kb) |
Type Of Material | Database/Collection of data |
Year Produced | 2019 |
Provided To Others? | Yes |
URL | https://springernature.figshare.com/articles/Additional_file_3_of_Systems_based_analysis_of_human_em... |
Description | Collaboration with Tocris |
Organisation | Bio-Techne Ltd |
Department | Tocris |
Country | United Kingdom |
Sector | Private |
PI Contribution | Planned collaboration to develop high though put screening for drugs enhancing chondrogenesis |
Collaborator Contribution | Targeted drug libraries, screening support and advice; Modified compounds |
Impact | Seeking joint funding |
Start Year | 2019 |
Description | Erasmus MC Rotterdam |
Organisation | Erasmus MC |
Country | Netherlands |
Sector | Hospitals |
PI Contribution | Collaboration including a month's research time at host institute, Consultancy for iPSC generation and differentiation. |
Collaborator Contribution | Collaboration including a month's research time at host institute |
Impact | Shared research skills and model exchange; collaboration on research programme |
Start Year | 2015 |
Description | GAG analysis 1 |
Organisation | Ben-Gurion University of the Negev |
Country | Israel |
Sector | Academic/University |
PI Contribution | We generate the cellular model , they may analyse GAGS |
Collaborator Contribution | Initiating |
Impact | initiating only |
Start Year | 2016 |
Description | GAG analysis with Keele/Oswestry |
Organisation | Keele University |
Department | School of Law |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | We have a protocol for chondrogenesis . Nicky Kuipper at Keele Oswestry will analyse GAGS in medium and cells for preliminary data for a grant application |
Collaborator Contribution | FACE and other analyses |
Impact | analyses of samples in progress |
Start Year | 2016 |
Description | Miltenyi |
Organisation | Miltenyi Biotec GmBH |
Country | Germany |
Sector | Private |
PI Contribution | We have submitted a large grant application to Arthritis Research Uk with Miltenyi. If successful they will contribute in kind support with cell sorting and GMP translationof our protocol for clinical therapy |
Collaborator Contribution | Cell sorting expertise and kits/antibodies/plates for FACs based cell sorting for enrichment of chondroprogenitors |
Impact | Too early |
Start Year | 2017 |
Description | Understanding regulation of chondrogenesis by Sirt1 |
Organisation | Hebrew University of Jerusalem |
Country | Israel |
Sector | Academic/University |
PI Contribution | Collaboration to understand epigenetic regulation of hESC chondrogenesis through regulation by histone deacetylases |
Collaborator Contribution | Training in CHIP technology for Post doc in host lab. Expertise in CHIP,CHIP-CHIP, epigentic modifificaiton and analysis,cartilage biology Exchange of reagents and knowledge. |
Impact | ARUK grant obtained |
Start Year | 2013 |
Description | CMFT Xmas lecture |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Xmas Royal Society-style lecture for Central Manchester NHS Foundation Trust "The Stem Cell Revolution". School visit requests |
Year(s) Of Engagement Activity | 2013 |
Description | Faraday Lecture Cambridge |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | Faraday Public Lecture |
Year(s) Of Engagement Activity | 2019 |
Description | Knutsford Sci bar |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Presentation and discussion on developments an uses in Pluripotent stem cell research. Discussed therpeutic uses in e,g, drug development anf testing and cell based therapy. |
Year(s) Of Engagement Activity | 2023 |
Description | Lancashire Humanists |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | Regional |
Primary Audience | Public/other audiences |
Results and Impact | 70 people attenced a public lecture on stem cell biology Requests for other talks to Humanist groups. |
Year(s) Of Engagement Activity | 2013 |
Description | Liverpool Medical Institue Symaposium on Stem Cell Regeneration and Osteoarthritic Tissue |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Talk on use of stem cells in orthopedics by Dr Chris Smith (Pdra) |
Year(s) Of Engagement Activity | 2019 |
Description | Patient information talk Manchester |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Patients, carers and/or patient groups |
Results and Impact | Informationa dn exchange talk with teh RUG group associated with a osteo and rheumatoid arthritis in Central Manchester Trust |
Year(s) Of Engagement Activity | 2019 |
Description | Radio 4 interview re 'Promising' stem cell trials for blindness |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Daniel Brison interviewed and commented on news story re stem cell therapies Raising public awareness |
Year(s) Of Engagement Activity | 2012 |
Description | Radio 4 interview with Mark Porter |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Sue Kimber interviewed on Radio 4 Case Notes programme re stem cell therapies Raised public awareness, led to doubled patient and GP interest in NWESCC |
Year(s) Of Engagement Activity | 2012 |
Description | STEM Cell Day |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Schools |
Results and Impact | Talk triggered questions and interest Students suggested they would like to apply for bio/biomed in Manchester |
Year(s) Of Engagement Activity | 2014 |
Description | School 6th form talk 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Atalk given to 5, 6th form groups about stem cells and medicine |
Year(s) Of Engagement Activity | 2019 |
Description | School 6th form talk 2019 |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Schools |
Results and Impact | Talk about Stem Cells and regenerative medicine to 5 6th form groups at local school |
Year(s) Of Engagement Activity | 2019 |
Description | Scibar Disbury |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Talk about the uses and developments in pluripotent stem cell biology anf the potential for drug testing and cell therapy |
Year(s) Of Engagement Activity | 2023 |
Description | Science Media Centre press conference |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | Yes |
Type Of Presentation | Keynote/Invited Speaker |
Geographic Reach | National |
Primary Audience | Media (as a channel to the public) |
Results and Impact | Press conference organised by SMC to discuss press release concerning submission of clinical grade embryonic stem cell lines to the UK Stem Cell Bank Interest from media, followup stories. Followup contacts from industry resulting directly from press release. |
Year(s) Of Engagement Activity | 2011 |
Description | South Africa public engagement |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Series of talks in cities and a rural community in South Africa to community, university and church groups |
Year(s) Of Engagement Activity | 2020 |
Description | Stem Cells and Regenerative medicine from chondrocytes to kidneys |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | Talk on Regenerative medicine to U3A members |
Year(s) Of Engagement Activity | 2018 |
Description | Stem cells magic for future medicine U3A |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Public/other audiences |
Results and Impact | U3A and other organisations in area Public engagement and discussion about future medicine |
Year(s) Of Engagement Activity | 2019 |
Description | What is Regenerative Medicine? |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Undergraduate students |
Results and Impact | A workshop to inform Undergraduates about what regenerative medicine is and how t can expand the possibiites for Medicine ( based on our successful workshop in 2017) |
Year(s) Of Engagement Activity | 2018 |
Description | What is Regenerative Medicine? |
Form Of Engagement Activity | Participation in an activity, workshop or similar |
Part Of Official Scheme? | No |
Geographic Reach | Local |
Primary Audience | Undergraduate students |
Results and Impact | Lay type presentation explaining what the opportunities are in the sector with exemplar talks form PhD students postdoctoral researchers and research fellows |
Year(s) Of Engagement Activity | 2017 |
Description | Women in Science Becoming the Best |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | Regional |
Primary Audience | Professional Practitioners |
Results and Impact | Dissemaination of information advice and support for women's role and leadership in scince |
Year(s) Of Engagement Activity | 2016 |