Proposal for a Human Embryonic Stem (ES) Cell Resource Centre

Lead Research Organisation: University of Sheffield
Department Name: Finance

Abstract

We aim to provide resources and training for other researchers planning to take up the study of human embryonic stem (ES) cells. At the same time we plan to develop new underpinning technologies to help facilitate research with these cells.
ES cells are derived from early human embryos and have the capacity to grow indefinitely in culture. At the same time they retain the ability to differentiate, or change, into all of the different cell types found in the human body. It is hoped can use this capacity of ES cells to develop new sources of cell types for replacing diseased or damaged tissues, or to develop new tools for understanding human development and the causes or different diseases.
The human ES cell field is young and the techniques for working with these cells are poorly developed. By providing resources for training investigators new to human ES cell research, and establishing new tools, we will help increase the capacity for new research that will underpin the future applications of human ES cells.
.

Technical Summary

We propose to establish a Human ES Cell Resource Centre to help accelerate progress with human Embryonic Stem (hES) cell research in the UK, by making readily available qualified to UK researchers human ES cell resources and expertise currently held in the Centre for Stem Cell Biology of the University of Sheffield. In particular, the Resource Centre would: i) provide rapid access to expertise and facilities to support short term pilot projects in hES cell biology, designed to obtain proof of concept and preliminary data to underpin further grant applications, ii) offer training in working with hES cells, iii) make the infrastructure for hES cell work available to specific, funded collaborative projects with researchers who have expertise and interests in other areas pertinent to hES cell research and its application, but who do not wish to establish that infra-structure themselves, iv) develop specific hES cell technologies that can be made available to the UK research community as a whole, v) set up, in conjunction with the National Stem Bank, a website and database, to collate and provide ready access to technical information and protocols developed in the Centre, and elsewhere, pertinent to future hES cell research, and vi) establish a program to evaluate the economic and social factors that will influence the future development of clinical applications of hES based research, including the public perception and ethical acceptability of current hES research and the potential economic impact in relation to different disease and patient groups. Technologies developed in the Centre would include: i) cryopreservation, ii) optimization of culture conditions and growth without feeders, iii) development of RNAi technologies for hES cells, iv) development of vectors to allow production of stable constitutive and conditional transfectants, v) development of homologous recombination strategies, and vi) development of new monoclonal antibodies to marker antigens for hES cells and their differentiated derivatives.

Publications

10 25 50
publication icon
Aflatoonian B (2006) Germ cells from mouse and human embryonic stem cells. in Reproduction (Cambridge, England)

publication icon
Furue MK (2008) Heparin promotes the growth of human embryonic stem cells in a defined serum-free medium. in Proceedings of the National Academy of Sciences of the United States of America

publication icon
International Stem Cell Initiative (2007) Characterization of human embryonic stem cell lines by the International Stem Cell Initiative. in Nature biotechnology

publication icon
Liew CG (2008) Stem cell therapy to treat diabetes mellitus. in The review of diabetic studies : RDS

 
Description BBSRC Project Grant
Amount £215,030 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 05/2007 
End 09/2010
 
Description BBSRC Project Grant (Identifying chemical agents that affect human embryonic stem cells in vitro and determining their molecular targets)
Amount £265,737 (GBP)
Funding ID BB/D006120/1 
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 02/2006 
End 02/2009
 
Description ESTOOLS Advances with Human Embryonic Stem Cells (12m euros across 23 participants)
Amount £427,826 (GBP)
Funding ID 18739 
Organisation European Commission 
Sector Public
Country European Union (EU)
Start 07/2006 
End 07/2010
 
Description MRC Research Grant
Amount £1,368,610 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 12/2007 
End 04/2013
 
Description MRC/ISCF
Amount £1,080,000 (GBP)
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 02/2006 
End 02/2011
 
Description UKIERI Collaboration grant
Amount £112,500 (GBP)
Organisation UK-India Education and Research Initiative (UKIERI) 
Sector Academic/University
Country United Kingdom
Start 11/2007 
End 03/2011
 
Description YCR Project Grant
Amount £166,700 (GBP)
Organisation Yorkshire Cancer Research 
Sector Charity/Non Profit
Country United Kingdom
Start 05/2008 
End 04/2011
 
Title Genetically modified human ES cell lines 
Description Human ES cell lines containing and expressing various transgenes including GFP and the tetrocyclin repressor protein 
Type Of Material Cell line 
Year Produced 2008 
Provided To Others? Yes  
Impact Tet-repressor sysgem is available for inducible knock-down of genes using shRNA 
 
Title Human ES cells 
Description Two new human ES cell lines were developed, Shef3 and Shef6 
Type Of Material Cell line 
Year Produced 2007 
Provided To Others? Yes  
Impact Human ES cell lines deposited to UK Stem Cell Bank and available for human ES cell research 
 
Description Cell banking 
Organisation National Institute for Biological Standards and Control (NIBSC)
Department UK Stem Cell Bank
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution Close interaction with UKSCB to facilitate the spread of expertise with human ES cell culture. Members of UKSCB have taught on training courses and staff members at Sheffield have provide advice with the UKSCB activities.
Collaborator Contribution Shared expertise and knowledge of working with hES cells.
Impact Successful annual training events have been held and substantial other collaborations have resulted from UKSCB involvement. PMID: 17572666.
 
Description Coffey - hES cells to retinal pigment cells 
Organisation University College London
Department Institute of Ophthalmology UCL
Country United Kingdom 
Sector Academic/University 
PI Contribution Using hES cells developed at CSCB.
Collaborator Contribution Using hES cells developed at CSCB.
Impact Collaboration with Prof. Coffey has led to the recognition that hES cells can readily differentiate to retinal pigment cells that potentially can be used for transplantation to cure macular degeneration. Prof. Coffey is using hEScells developed at the Centre for Stem Cell Biology for these experiments aimed at eventual clinical trials. Staff from CSCB have contributed expertise and reagents, etc as well as training to support his on-going work.
Start Year 2007
 
Description Dunne - Development of pancreatic cells for treating diabetes 
Organisation University of Manchester
Department Faculty of Life Sciences
Country United Kingdom 
Sector Academic/University 
PI Contribution Funds were jointly awarded by the JDRF to develop basic aspects of hES cell biology that could eventually facilitate their use in developing pancreatic cells for treatment of disease.
Collaborator Contribution Joint grant from JDRF supported the development of basic aspects of hES cell biology.
Impact PMID 18335054
 
Description Enver - behaviour of hES cells 
Organisation Oxford University Hospitals NHS Foundation Trust
Country United Kingdom 
Sector Academic/University 
PI Contribution The work has led to the analysis of the behaviour of hES cells and their adaptation to culture, which has parallels with cancer development from stem cells. We have been able to assist Prof. Enver in establishing his own hES cell program for CSCB has provided training, protocols and materials (eg. feeder cells, antibodies, etc).
Collaborator Contribution Analysis of the behaviour of stem cells.
Impact Enver T, Soneji S, Joshi C, Iborra F, Orntoft T, Thykjaer T, Maltby E, Smith K, Abu Dawd R, Matin M, Gokhale P, Draper JS, Andrews PW (2005) Cellular differentiation hierarchies in normal and culture adapted human embryonic stem cells. Human Mol Genet. 14: 1-12.
 
Description Lotte - Relationships between hES & EC cells 
Organisation National Institute for Biological Standards and Control (NIBSC)
Country United Kingdom 
Sector Public 
PI Contribution The project is facilitated by the infrastructure of the CSCB, notably from the panel of human EC cells that are maintained in Sheffield, as well as antibodies, reagents and panel of hES cell lines.
Collaborator Contribution Exploring relationships between hES and embryonal carcinoma (EC) cells from germ cell tumours.
Impact Skotheim RI, Autio R, Lind GE, Kraggerud SM, Andrews PW, Monni O, Kallioniemi O, Lothe RA. 2006 Novel genomic aberrations in testicular germ cell tumors by array-CGH, and associated gene expression changes. Cell Oncol. 28:315-326
Start Year 2006
 
Description NCBS, India - hES cell training course 
Organisation National Centre for Biological Science (NCBS)
Country India 
Sector Academic/University 
PI Contribution Staff members of CSCB have contributed to two practical courses in working with hES cells, held at the NCBS, the first sponsored by the Royal Society and the FCO. A member of this group has spent 12 days at NCBS, helping with cell culture techniques and growing hES cells.
Collaborator Contribution Interactions have led to continued dialogue and establishment of an on-going collaboration funded by a UKIERI grant.
Impact Collaboration continues and in part supported by a UKIERI award. A member of the India team is expected to spend up to 3 months in Sheffield before the end of 2010.
Start Year 2007
 
Description Suarez - project on epigenetic regulation 
Organisation Hospital Covadonga Oviedo
Department Immunology Service
Country Spain 
Sector Hospitals 
PI Contribution Dr Suarez attended a training day held at CSCB where staff provided advice, training and expertise in working with hES cells.
Collaborator Contribution A project was initiated focusing on epigenetic regulation of MHC expression and regulation in hES cells.
Impact PMID 188207279
Start Year 2007
 
Description Timmermans & Vandekerckhove - Generation of T cells 
Organisation University of Ghent
Country Belgium 
Sector Academic/University 
PI Contribution Staff worked together, offering advice and expertise.
Collaborator Contribution Collaborations on the generation of T cells in vitro from hES cells.
Impact Paper submitted.
Start Year 2008
 
Description Cheltenham Science Festival 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Schools
Results and Impact Presentations and posters given at this event, aimed primarily at pupils from schools and colleges in the local area, promoting a career in science. 5 day event. Positive feedback from students.

Information provided to high school students
Year(s) Of Engagement Activity 2008
 
Description ESTOOLS Annual Public Meeting, Brno 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Primary Audience Public/other audiences
Results and Impact Public meeting held at the end of the ESTOOLS FP6 project Annual Meeting, attended by 150 members of the public, mainly from local Czech people but also invited speakers and members of the consortium. 1 day meeting. Positive feedback - recorded on the ESTOOLS website www.estools.org.

The interest generated by those attendance has proven the need for more events such as this, to keep the public informed. Also broadcast through Czech TV and radio coverage.
Year(s) Of Engagement Activity 2007
 
Description ESTOOLS Annual Public Meeting, Budapest 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? Yes
Primary Audience Public/other audiences
Results and Impact Annual Scientific Meeting of ESTOOLS an FP6 Consortium co-ordinated by the PI and CSCB in Sheffield

Public meeting held at the end of the ESTOOLS FP6 project Annual Meeting, attended by 150 members of the public, mainly from local Hungarian people but also invited speakers and members of the consortium. 1 day meeting. Positive feedback - recorded on the ESTOOLS website www.estools.org. Conveyed information on human ES cell research to non-scientists in Hungary.
Year(s) Of Engagement Activity 2008
 
Description Espergaerde Upper Secondary School 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Primary Audience Schools
Results and Impact Attended by 22 school-aged children from a school in Denmark where a series of short talks, and question/answer sessions were held. Positive feedback from both pupils and teachers.

Provided information on human ES cell research to a visiting class of Danish High School students
Year(s) Of Engagement Activity 2008
 
Description Euronews broadcast 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Primary Audience Media (as a channel to the public)
Results and Impact Interview held with PI and MEP on working with human embryonic stem cells, broadcasted by Euronews, Brussels.

Link to European Parliament
Year(s) Of Engagement Activity 2007
 
Description Local school visit 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Primary Audience Schools
Results and Impact Attended by 25 school children aged 16. Talks given on stem cells and what they are, the derivation of hES cells, international aspects of science and undergraduate degrees at the University of Sheffield, followed by demonstrations and tour of lab facilities.

Provided information on human ES cell research to local Sheffield High School students
Year(s) Of Engagement Activity 2007,2008
 
Description Media (as a channel to the public) 
Form Of Engagement Activity A press release, press conference or response to a media enquiry/interview
Part Of Official Scheme? No
Primary Audience Media (as a channel to the public)
Results and Impact Cooperation with representatives of the media, provided interviews and information, partly through the Science Media Centre, to inform journalists of the work.

Unknown
Year(s) Of Engagement Activity 2006,2007
 
Description School visit - Denmark school 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Primary Audience Schools
Results and Impact Visit by a group of 22 children from an upper secondary school.

Unknown
Year(s) Of Engagement Activity 2007
 
Description School visit - Sheffield 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? Yes
Primary Audience Schools
Results and Impact Talks given on stem cells and what they are, the derivation of hES cells, international aspects of science and undergraduate degrees at the University of Sheffield, followed by demonstrations and tour of lab facilities.

Further request to do the same in the next year as the pupils found it of benefit.
Year(s) Of Engagement Activity 2007
 
Description Science week activities 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Primary Audience Schools
Results and Impact Staff giving lectures, workshops and presentations in schools.

Unknown
Year(s) Of Engagement Activity 2006,2007,2008