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.

Publications

10 25 50
 
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 HFEA Information for Quality programme
Geographic Reach National 
Policy Influence Type Participation in advisory committee
Impact acting as advisor to Human Fertilisation and Embryology Authority Information for quality programme which aims to improve regulatory oversight of the field including stem cell derivation, and improve information to patients and for delivery of clinical IVF services.
 
Description Influencing policy towards patenting of discoveries using hESC lines
Geographic Reach Europe 
Policy Influence Type Membership of a guideline committee
 
Description Member of TERMIS Scientific Advisory Board
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
Description Membership of HFEA's Scientific and Clinical Advances committee
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
Impact Advising the HFEA on changes in regulation on ART practice, embryology, embryonic stem cell biology
 
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 Stem Cells for Safer Medicine Panel Member
Geographic Reach National 
Policy Influence Type Participation in a advisory committee
 
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 06/2014 
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 08/2015 
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 10/2013 
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 05/2015 
End 04/2017
 
Description NIHR Clinical fellowship
Amount £270,000 (GBP)
Organisation National Institutes of Health (NIH) 
Sector Public
Country United States
Start 06/2016 
End 05/2021
 
Description Sparking Impact
Amount £10,000 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 07/2014 
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 09/2014 
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 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 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 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