Bulk culture of commercially viable embryonic stem cells.
Lead Research Organisation:
University of Manchester
Department Name: Dentistry
Abstract
Dr Ward has developed and patented an enabling technology that permits the growth of embryonic stem cells in high density 3D cultures without the need for potentially harmful mouse feeder lines and expensive growth factors. The technology helps maintain ES cells in an undifferentiated state for prolonged periods (at least 30 days) and can significantly reduce the technical burden associated with current methods. By offering a route to simple, cost effective large volume culture of both mouse and human ES cells we will help to transform the utility of stem cells and widen their use as research tools and ultimately as therapeutic treatments of degenerative diseases. The objectives of this study are:- 1) Optimize and refine methods fro 3D stem cell culture; 2) Construct ES cell lines and media formulations for sale to the research community; 3) Produce a 'best practice' translatable manufacturing process; 4) To promote and market the technology to potential development partners and licensees.
People |
ORCID iD |
| Christopher Ward (Principal Investigator) |
Publications
Dou R
(2015)
High throughput cryopreservation of cells by rapid freezing of sub-µl drops using inkjet printing--cryoprinting.
in Lab on a chip
Eastham AM
(2007)
Epithelial-mesenchymal transition events during human embryonic stem cell differentiation.
in Cancer research
Hawkins K
(2012)
E-cadherin and, in its absence, N-cadherin promotes Nanog expression in mouse embryonic stem cells via STAT3 phosphorylation.
in Stem cells (Dayton, Ohio)
Hawkins K
(2014)
Novel Cell Lines Isolated From Mouse Embryonic Stem Cells Exhibiting De Novo Methylation of the E-Cadherin Promoter
in Stem Cells
Keramari M
(2010)
Sox2 is essential for formation of trophectoderm in the preimplantation embryo.
in PloS one
Mohamet L
(2014)
Familial Alzheimer's disease modelling using induced pluripotent stem cell technology.
in World journal of stem cells
Mohamet L
(2011)
Loss of function of e-cadherin in embryonic stem cells and the relevance to models of tumorigenesis.
in Journal of oncology
Segal JM
(2017)
Novel peptides for deciphering structural and signalling functions of E-cadherin in mouse embryonic stem cells.
in Scientific reports
Soncin F
(2011)
The function of e-cadherin in stem cell pluripotency and self-renewal.
in Genes
| Description | Peptides developed for the culture of human and mouse ES cells in suspension culture |
| Exploitation Route | Spin-out company formed to exploit project outcomes |
| Sectors | Healthcare Manufacturing including Industrial Biotechology Pharmaceuticals and Medical Biotechnology |
| Description | 3 x patents filed from this technology and a spin-out company formed |
| First Year Of Impact | 2008 |
| Sector | Healthcare,Manufacturing, including Industrial Biotechology,Pharmaceuticals and Medical Biotechnology |
| Impact Types | Societal Economic |
| Description | EPSRC Stem cell strategy development panel. Royal Society, London. Panel member. 16th March 2009. |
| Geographic Reach | National |
| Policy Influence Type | Participation in a guidance/advisory committee |
| Impact | Stem cell call funded by EPSRC |
| Description | BBSRC Pathfinder award |
| Amount | £13,319 (GBP) |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2012 |
| End | 05/2012 |
| Description | BBSRC follow-on-fund |
| Amount | £216,979 (GBP) |
| Funding ID | BB/K020277/1 |
| Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2013 |
| End | 04/2015 |
| Description | Crack-It UnTangle NC3Rs |
| Amount | £81,956 (GBP) |
| Funding ID | 35529-259127 |
| Organisation | National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2013 |
| End | 06/2014 |
| Description | DPUK: Integrated Dementia Research Environment |
| Amount | £6,091,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 05/2015 |
| End | 09/2016 |
| Description | EPSRC Stem cell call |
| Amount | £2,637,207 (GBP) |
| Funding ID | EP/H046070/1 |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2011 |
| End | 12/2014 |
| Description | IAA Concept study |
| Amount | £62,537 (GBP) |
| Organisation | Engineering and Physical Sciences Research Council (EPSRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 03/2015 |
| End | 09/2015 |
| Description | Microfluidic Modulation of Embryonic Stem Cell Differentiation in Well-Defined Microscopic Flow (KTA Award 104: 2010-2011). |
| Amount | £35,243 (GBP) |
| Organisation | University of Sheffield |
| Department | EPSRC KTA Knowledge Transfer Account |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 03/2010 |
| End | 04/2011 |
| Description | Neuratect: Human iPSC neuronal network platform for neurotoxicity screening |
| Amount | £100,000 (GBP) |
| Funding ID | NC/C014105/1 |
| Organisation | National Centre for the Replacement, Refinement and Reduction of Animals in Research (NC3Rs) |
| Sector | Public |
| Country | United Kingdom |
| Start | 12/2014 |
| End | 06/2015 |
| Description | Proximity to Discovery Secondment Grant |
| Amount | £57,000 (GBP) |
| Organisation | Medical Research Council (MRC) |
| Sector | Public |
| Country | United Kingdom |
| Start | 08/2015 |
| End | 05/2016 |
| Description | UK UKDP: Integrated Dementia Research Environment |
| Amount | £2,329,271 (GBP) |
| Funding ID | MR/M009076/1 |
| Organisation | Medical Research Council (MRC) |
| Department | Medical Research Foundation |
| Sector | Charity/Non Profit |
| Country | United Kingdom |
| Start | 08/2015 |
| End | 09/2016 |
| Description | University of Manchester, The |
| Amount | £117,000 (GBP) |
| Funding ID | PoP fund |
| Organisation | University of Manchester |
| Sector | Academic/University |
| Country | United Kingdom |
| Start | 03/2012 |
| End | 09/2013 |
| Title | Differentiation of iPSCs to neural progenitor cells |
| Description | Small peptides developed during this grant has been used to derive homogeneous populations of neural progenitor cells from iPSCs (human and mouse). |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2014 |
| Provided To Others? | Yes |
| Impact | NC3Rs Phase 1 grant award for the development of a Tau cell model |
| Title | Peptide development |
| Description | Small peptides have been developed during this grant that enable modification of gene transcript expression in embryonic stem cells |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2012 |
| Provided To Others? | Yes |
| Impact | Several papers published by me and collaborators published |
| Title | Suspension culture of ES/iPS cells |
| Description | Small peptides developed during this grant that allows the culture of iPSCs and ES cells (human and mouse) in suspension culture. |
| Type Of Material | Technology assay or reagent |
| Year Produced | 2010 |
| Provided To Others? | Yes |
| Impact | Industry collaborations with Lonza. |
| Title | Microarray analysis of E-cadherin inhibition in cells |
| Description | Microarray analysis of E-cadherin inhibition in mouse and human ES cells and mammary epithelial tumour cells has been analysed |
| Type Of Material | Database/Collection of data |
| Year Produced | 2009 |
| Provided To Others? | Yes |
| Impact | Evidence that E-cadherin plays a major part in regulating signalling pathways, proliferation and apoptosis in ES and tumour cells |
| Description | Dr Richard Wade-Martins |
| Organisation | University of Oxford |
| Department | Department of Biochemistry |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Confidential |
| Collaborator Contribution | Confidential |
| Impact | Manuscript in preparation |
| Start Year | 2013 |
| Description | Imagen-biotech |
| Organisation | Imagen Biotech |
| Country | United Kingdom |
| Sector | Private |
| PI Contribution | Provision of iPS cells derived from Alzheimer's disease patients for use in drug screening applications. |
| Collaborator Contribution | Development of an Alzheimer's disease drug screening platform |
| Impact | Technology still in development |
| Start Year | 2012 |
| Description | Prof Ben Whalley |
| Organisation | University of Reading |
| Department | School of Pharmacy Reading |
| Country | United Kingdom |
| Sector | Academic/University |
| PI Contribution | Confidential |
| Collaborator Contribution | Confidential |
| Impact | Manuscript currently being written |
| Start Year | 2013 |
| Title | CELL CULTURE |
| Description | There is provided a method of retarding differentiation of a biological cell, the method comprising culturing the cell in the presence of an inhibitor of E-cadherin activity. The method is particularly advantageous in retarding the differentiation of stem or progenitor cells, and allows suspension culture of such cells in a manner that enables large scale expansion of cell populations. There is also provided a stem or progenitor cell comprising a construct encoding an inhibitor of E-cadherin activity; and a cell culture medium, for use in the retardation of biological cell differentiation, comprising an inhibitor of E-cadherin activity. |
| IP Reference | WO2007088372 |
| Protection | Patent granted |
| Year Protection Granted | 2007 |
| Licensed | Yes |
| Impact | Further E-cadherin inhibiting peptides have been developed and patented. |
| Title | CELL DIFFERENTIATION |
| Description | Provided is a method of producing neural precursor cells, in which an inhibitor of E-cadherin activity is provided to a population of the cells having neural potential, cell stress is induced among the population of cells; and the surviving cells are cultured until neural precursor cells are produced. Also provided is a method of adapting a cell in vitro for therapeutic use, in which an inhibitor of E-cadherin activity is provided to a population of cells having neural potential, cell stress is induced among the population of cells, and the surviving cells are cultured until neural precursor cells are produced. This method may optionally additionally involve culturing the neural precursor cells until neural cells are produced and formulating the neural precursor cells or neural cells in a composition suitable for administration to a patient. The invention also provides cells produced by these methods. The methods may be practiced on stem cells, particularly iPSCs. The cells and methods have utility in applications including stratified medicine. |
| IP Reference | WO2014072720 |
| Protection | Patent application published |
| Year Protection Granted | 2014 |
| Licensed | Yes |
| Impact | Non-exclusive research licence awarded to Imagen-Biotech Ltd |
| Title | Patent application 2017 |
| Description | The work from this grant has enabled a patent application to be filed on the identification of biomarkers for the automated analysis of abnormal epithelium |
| IP Reference | P33974GB1/RSM |
| Protection | Patent application published |
| Year Protection Granted | 2017 |
| Licensed | Commercial In Confidence |
| Impact | Patent was filed February 2017 |
| Title | Alzheimer's disease diagnostic |
| Description | Alzheimer's disease diagnostic |
| Type | Diagnostic Tool - Non-Imaging |
| Current Stage Of Development | Refinement. Non-clinical |
| Year Development Stage Completed | 2012 |
| Development Status | Actively seeking support |
| Impact | None |
| Company Name | Stratastem |
| Description | Stratastem develops therapeutics for Alzheimer's disease based on neural stem cells, as well as diagnostics for the disease that detect changes in neuronal pathology. |
| Year Established | 2012 |
| Impact | Biotech Start-up |
| Website | http://stratastem.weebly.com |
| Description | Abcam Stem Cell Conference 2009, Antigua. 19th to 22nd of November 2009. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Talk sparked questions and discussion New collaborations identified |
| Year(s) Of Engagement Activity | 2009 |
| Description | BBSRC Next Generation Conference - commercialisation of research. November 2008. |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | Yes |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Discussion of commercialisation of research Potential commercial collaborators identified |
| Year(s) Of Engagement Activity | 2008 |
| Description | Chair/keynote speaker: 'The 2014 Regenerative Medicine Event: Stem Cell Reprogramming' meeting |
| Form Of Engagement Activity | Scientific meeting (conference/symposium etc.) |
| Part Of Official Scheme? | No |
| Type Of Presentation | keynote/invited speaker |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Talk sparked questions and discussion Potential collaborators identified |
| Year(s) Of Engagement Activity | 2014 |
| Description | EPSRC Stem cell strategy development panel. Royal Society, London. Panel member. 16th March 2009 |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | Yes |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Discussion of EPSRC stem cell strategy Final recommendations presented |
| Year(s) Of Engagement Activity | 2009 |
| Description | High throughput screening strategies for neuromuscular disease. TREAT-NMD. Netherlands. 27th Feb - 1st March 2009. |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | Yes |
| Geographic Reach | International |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Discussion of development of tools that industry, clinicians and scientists need to bring novel therapeutic approaches through preclinical development and into the clinic, and on establishing best-practice care for neuromuscular patients worldwide. Report produced |
| Year(s) Of Engagement Activity | 2009 |
| Description | Invited lecture |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | Regional |
| Primary Audience | Professional Practitioners |
| Results and Impact | MSCA Annual Scientific Meeting, 8th December 2015, Sheffield University, UK. |
| Year(s) Of Engagement Activity | 2015 |
| Description | Invited lecture: Enabling Technologies for Stem Cell and Regenerative Medicine Research. Cambridge 28th November 2012. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Talk sparked questions and discussion afterwards Industry collaborators identified |
| Year(s) Of Engagement Activity | 2012 |
| Description | Invited lecture: Keystone Symposia A8 2011 Epithelial Plasticity and Epithelial to Mesenchymal Transition, Jan 21 - Jan 26, 2011, Vancouver, British Columbia. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Talk sparked questions and discussion afterwards. Academic and commercial collaborators identified |
| Year(s) Of Engagement Activity | 2011 |
| Description | Invited lecture: Stem Cells in Drug Discovery conference, 2-3 June 2015, Cambridge University, UK |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Stem Cells in Drug Discovery conference, 2-3 June 2015, Cambridge University, UK |
| Year(s) Of Engagement Activity | 2015 |
| Description | Invited research talk. Uppsala University, Sweden. 13th May 2015. |
| Form Of Engagement Activity | A talk or presentation |
| Part Of Official Scheme? | No |
| Geographic Reach | International |
| Primary Audience | Professional Practitioners |
| Results and Impact | Invited research talk. Uppsala University, Sweden. 13th May 2015. |
| Year(s) Of Engagement Activity | 2015 |
| Description | Maths in Medicine Workshop. Keele University 10th-14th Sept 2012 |
| Form Of Engagement Activity | Participation in an activity, workshop or similar |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Other academic audiences (collaborators, peers etc.) |
| Results and Impact | Mathematical modelling of microarray data achieved. Further collaborations identified |
| Year(s) Of Engagement Activity | 2012 |
| Description | TSB Stratified Medicine strategy on neurodegenerative diseases workshop. October 2013 |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | Yes |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Discussion/workshop on TSB Stratified Medicine strategy on neurodegenerative diseases Recommendations made |
| Year(s) Of Engagement Activity | 2013 |
| Description | The role of BBSRC, TSB and MRC in funding commercial initiatives. BBSRC HQ. Panel member. August 2008 |
| Form Of Engagement Activity | A formal working group, expert panel or dialogue |
| Part Of Official Scheme? | No |
| Geographic Reach | National |
| Primary Audience | Policymakers/politicians |
| Results and Impact | Workshop discussing the roles of BBSRC, TSB and MRC in funding commercial initiatives. Recommendations made |
| Year(s) Of Engagement Activity | 2008 |