Expandable Clinical Grade Feeder Cells for hESc Derivation
Lead Research Organisation:
University of Manchester
Department Name: Life Sciences
Abstract
We aim to generate an inexhaustible supply of immortalised clinical grade human dermal fibroblasts (hDFs) for derivation of cGMP hESc lines. Human Embryonic stem cells (hESc) have great potential for use in clinical therapies but current hESc lines have not been generated under conditions suitable for clinical use. We will exploit our successful TSB-funded feasibility study to generate suitable immortalised human dermal fibroblasts (hDFs) for derivation of cGMP hESc lines. We will immortalise 2 primary (clinical grade) hDF lines, already shown to support culture and derivation of cGMP hESc lines in a unique media system, using a method shown by us to generate hESc-supportive feeder cells at the research level. The immortalised cells will be tested for derivation of new cGMP hESc lines and will provide a supply of marketable cGMP feeder cells for use in generating hESc for therapy.
Technical Summary
We aim to generate an inexhaustible supply of immortalised clinical grade human dermal fibroblasts (hDFs) for derivation of cGMP hESc lines. Human Embryonic stem cells (hESc) have great potential for use in clinical therapies but current hESc lines have not been generated under conditions suitable for clinical use. We will exploit our successful TSB-funded feasibility study to generate suitable immortalised human dermal fibroblasts (hDFs) for derivation of cGMP hESc lines. We will immortalise 2 primary (clinical grade) hDF lines, already shown to support culture and derivation of cGMP hESc lines in a unique media system, using a method shown by us to generate hESc-supportive feeder cells at the research level. The immortalised cells will be tested for derivation of new cGMP hESc lines and will provide a supply of marketable cGMP feeder cells for use in generating hESc for therapy.
Planned Impact
HESc are envisioned to play a major future role in the RM industry with market potentials in the region of $100 billion (MaRS report 2009). For this impact to be realised, of the many advances needed, one critical step is the ability to derive and grow clinical grade hESc which can be targeted to desired target cells. We seek to fill this gap in the RM market by producing xeno-free immortalised human feeder cells of validated ability to support derivation of hESc under stringent clinically acceptable conditions. Since there are no commercial sources of expandable xeno-free cGMP human feeder cells suitable for hESc growth and derivation that can be used as an alternative, what we propose is a unique opportunity to enhance UK and Europe's RM and possibly that outside Europe. Biotime (US) market only animal product-exposed hDFs which are not immortalised and thus not a significantly expandable supply as they carry the risk of losing their supportive ability with increased expansion. Our expandable cells will likely also function for the generation and culture of ES-like cells derived from somatic tissue (induced pluripotent somatic, ips, cells) which might form an alternative source of tissue for clinical therapy in the future. Critically, the further development of the hDF feeder lines through our immortalisation method will lead to a unique and fully expandable source of cells for commercial exploitation and this will be promoted and marketed commercially through the activities of XCellR8.
People |
ORCID iD |
Susan Kimber (Principal Investigator) | |
Daniel Brison (Co-Investigator) |
Publications
Villarin BL
(2015)
Polymer Supported Directed Differentiation Reveals a Unique Gene Signature Predicting Stable Hepatocyte Performance.
in Advanced healthcare materials
Description | We generated untransfected and immortlised human fibroblast feeders suitable for clinical grade pluripotent stem cell support and maintenace, which are used by us and the UKSTEM cell bang a swellas in other research organisations. |
Exploitation Route | To support GMP grade pluripotent stem cells for clinical use |
Sectors | Healthcare |
Description | Our validation of feeder cells allowed these to be used by UK Stem Cell Bank for support of other hESC GMP lines as well as our own |
First Year Of Impact | 2011 |
Sector | Healthcare |
Impact Types | Economic |
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 | BBSRC icase studentship (with Argo) |
Amount | £110,000 (GBP) |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2014 |
End | 12/2017 |
Description | Chondrocytes from clinical grade embryonic stem cells |
Amount | £793,000 (GBP) |
Funding ID | MR/L004992/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 05/2014 |
End | 05/2017 |
Description | Diabetes UK |
Amount | £570,000 (GBP) |
Organisation | Diabetes UK |
Sector | Charity/Non Profit |
Country | United Kingdom |
Start | 11/2015 |
End | 10/2018 |
Description | EME - EFREEZE |
Amount | £700,000 (GBP) |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 07/2015 |
End | 07/2018 |
Description | EME - HaBSelect |
Amount | £1,000,000 (GBP) |
Funding ID | EME/11/14/34 |
Organisation | National Institute for Health Research |
Sector | Public |
Country | United Kingdom |
Start | 01/2014 |
End | 12/2015 |
Description | EpiHealthNet |
Amount | € 285,607 (EUR) |
Funding ID | 317146 |
Organisation | European Commission |
Department | Seventh Framework Programme (FP7) |
Sector | Public |
Country | European Union (EU) |
Start | 09/2013 |
End | 09/2016 |
Description | MRC project grant |
Amount | £1,290,000 (GBP) |
Funding ID | MR/M017354/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 04/2015 |
End | 04/2017 |
Description | NIHR Clinical fellowship |
Amount | £270,000 (GBP) |
Organisation | National Institutes of Health (NIH) |
Sector | Public |
Country | United States |
Start | 05/2016 |
End | 05/2021 |
Description | Sparking Impact |
Amount | £10,000 (GBP) |
Organisation | Biotechnology and Biological Sciences Research Council (BBSRC) |
Sector | Public |
Country | United Kingdom |
Start | 06/2014 |
End | 12/2014 |
Description | Toxicology programme |
Amount | £80,000 (GBP) |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 01/2015 |
End | 12/2018 |
Description | UK national ART cohort - Population and Systems Medicine Board |
Amount | £200,000 (GBP) |
Funding ID | MR/L020335/1 |
Organisation | Medical Research Council (MRC) |
Sector | Public |
Country | United Kingdom |
Start | 08/2014 |
End | 08/2016 |
Title | Six Clinical grade Manchester hESC lined completed due diligence and made avialble by UKSCB |
Description | Manchester Clinical grade hESCs now registered as EUCTD compliant and launched by Stem Cell bank |
Type Of Material | Model of mechanisms or symptoms - in vitro |
Year Produced | 2017 |
Provided To Others? | Yes |
Impact | Provision at research grade lines in in 2015. Lead to several papers from Hay and Kunath groups. Now available as clinical grade though UKSCB |
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 |
Description | Cell and Gene Therapy Catapult |
Organisation | Cell and Gene Therapy Catapult |
Country | United Kingdom |
Sector | Private |
PI Contribution | The Cell and Gene Therapy Catapult will validate the biomarkers included in our Patent derived form the MRC MiCA grant with TEL and my MRC CiC award |
Collaborator Contribution | They will test the markers on the secretome of further pluripotent stem cells to the 5+ we have tested to date. |
Impact | None yet |
Start Year | 2020 |
Description | Randox |
Organisation | Randox Laboratories |
Country | Global |
Sector | Private |
PI Contribution | Randox have not delivered on our collaboration to validate secretome biomarkers for eevaluation of pluripotency. We have therfor with drawn from the collaboration and moved to another collaborator. |
Collaborator Contribution | Collaboration was to be in antibodies and antibody related know how and to validate our biomarkers in their systems. |
Impact | CiC applicaion obtained but due to non delivery fdid not pursue further grant funding. |
Start Year | 2017 |
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 | Guardian newspaper article on ART child health |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Guardian newspaper article on ART child health |
Year(s) Of Engagement Activity | 2015 |
Description | Invited lecture to EU Student Parliament debate on embryo research |
Form Of Engagement Activity | A talk or presentation |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Undergraduate students |
Results and Impact | Invited lecture to EU Student parliament debate on human embryo research including embryonic stem cell derivation, in Salford, UK |
Year(s) Of Engagement Activity | 2016 |
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 | Membership of HFEA's Information for Quality Programme |
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 | Membership of HFEA's Information for Quality Programme |
Year(s) Of Engagement Activity | 2015 |
Description | Membership of HFEA's Scientific and Clinical Advances Advisory Committee |
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 | Membership of HFEA's Scientific and Clinical Advances Advisory Committee |
Year(s) Of Engagement Activity | Pre-2006,2006,2007,2008,2009,2010,2011,2012,2013,2014,2015,2016 |
Description | New Scientist Article on ART child health |
Form Of Engagement Activity | A press release, press conference or response to a media enquiry/interview |
Part Of Official Scheme? | No |
Geographic Reach | International |
Primary Audience | Public/other audiences |
Results and Impact | Interview for article in New Scientist on research into ART child health |
Year(s) Of Engagement Activity | 2016 |
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 | 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 |