Derivation of clinical grade embryonic stem cell lines

Lead Research Organisation: King's College London
Department Name: Reproduction and Endocrinology

Abstract

Human embryonic stem (hES) cells can be isolated from early (6 day old) developing embryos which have been grown in the laboratory as part of, or surplus to some kinds of IVF treatment. Under certain conditions, these cells can be made to develop into different kinds of tissues, such as nerve cells or pancreatic cells which it is hoped in the future, may be useful in treating degenerative diseases such as Parkinson s disease and diabetes, or in spinal injuries by replacing the diseased or damaged cells with healthy hES cells which have been grown in the laboratory. The number of hES cell lines that have been developed worldwide that are suitable for clinical use is still very limited. Further research is required to find out the best means to grow them in ways that will allow them to be safe for clinical use which is the purpose of this grant. All stem cell derivation from embryos is strictly monitored in the UK and requires a licence from the Human Fertilisation and Embryology Authority (HFEA). In compliance with conditions of our HFEA licence, samples of any suitable stem cell lines developed will be sent to the UK Stem Cell Bank from where they are made available to research scientists in the UK and abroad through the MRC Stem Cell Steering Committee, and if suitable, for further preparation in the UKSCB for clinical use. With the Assisted Conception Unit (ACU) at Guy s, we have developed ethical ways of obtaining embryos for deriving stem cell lines that may be suitable for clinical use, especially from couples who have successfully undergone IVF treatment and have additional embryos in frozen storage which they no longer wish to use in their own treatment, nor wish to donate to other individuals. Rather than destroy them, patients often prefer to donate them for stem cell or other worthwhile research.

Technical Summary

The development and support of the UK stem cell bank is a clear signal of the government?s commitment to support both local and international research in stem cell research, and to the development of lines suitable for clinical use.
Although there have been important advances in the generation of hES, the derivation of lines for human use is tempered by the stringent requirements and methodological changes needed to meet GMP production standards. These include unequivocal permission from embryo donors for use of their embryos for therapeutic purposes without restrictions or financial claim, clear provenance of embryos including history, infectious agent of the donors, and documentation assuring traceability through the various stages from fertilization, though culture to blastocyst, and where indicated, cryopreservation. There also need to be changes to the methods for isolation of inner cell masses from blastocysts, moving away from the animal feeder layers for derivation and growth, and the use of more clearly defined media free of animal products.
Key to successful hES generation is access to human embryos in vitro able to develop to the blastocyst stage and beyond, and suitable facilities to derive under conditions compliant with the EUTCD and the requirements of the HTA. Ethical access to good quality embryos has been facilitated through the large and successful assisted conception unit and PGD programme at Guy s Hospital where over 1000 cycles are performed annually. In addition, through our nurse coordinator funded by MRC, we have set up a strong collaboration with 9 local NHS and private IVF units to provide cryopreserved embryos surplus to patients therapeutic need and suitable for stem cell research. We have also secured an investment of #4m from the MRC, KCL, the Guys and St Thomas? Charity and the Trust, towards the build of a new assisted conception unit on the 11th floor of the Guy?s tower, to house IVF treatment facilities, PGD laboratories and a two-room GMP stem cell suite leading directly off the IVF laboratory, due for completion in July 2008. It is our intention to utilise these facilities to generate, grown and characterise under GMP conditions, embryonic stem cell lines suitable for deposit in the UK Stem Cell Bank as clinical grade lines. In response to this strategic call we are applying for staff, equipment and supplies to enable us fulfill this aim.

Publications

10 25 50
 
Description Advisory Committee on Safety of Cells Tissues and Organs
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in advisory committee
Impact Member advising on testing and use of reproductive and stem cell tissues.
 
Guideline Title ESHRE guidelines on practice of PGD
Description ESHRE PGD Guideline
Geographic Reach Europe 
Policy Influence Type Citation in clinical guidelines
Impact Revision of Guideline to influence standards and practice of preimplantation genetic diagnosis and preimplantation genetic screening which will form the basis of other documents and compliance with EU directives
 
Description Joint committee on the Human Tissue and Embryos (Draft) Bill
Geographic Reach National 
Policy Influence Type Gave evidence to a government review
Impact Contributed to the demise of joint HFEA/HTA ALB to be called RATE. Remained as separate bodies and stem cell derivation remained under HFEA
 
Description Progress Educational Trust Advisory Board
Geographic Reach National 
Policy Influence Type Participation in advisory committee
 
Description Route Map for Stem Cell Regulation
Geographic Reach Multiple continents/international 
Policy Influence Type Participation in a national consultation
Impact Joint meeting of regulators to simplify processing of stem cell applications through HFEA, HTA, MHRA for clinical application
 
Description MRC Research Grant (G0701172)
Amount £600,000 (GBP)
Funding ID G0701172 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 02/2009 
End 01/2012
 
Description MRC Research Grant (G0801061)
Amount £484,420 (GBP)
Funding ID G0801061 
Organisation Medical Research Council (MRC) 
Sector Public
Country United Kingdom
Start 04/2009 
End 03/2012
 
Description Refurbishment of IVF lab and stem cell laboratories
Amount £1,500,000 (GBP)
Organisation King's College London 
Sector Academic/University
Country United Kingdom
Start 01/2007 
End 12/2008
 
Description Welcome biomedical ethics strategic award
Amount £800,000 (GBP)
Organisation Wellcome Trust 
Sector Charity/Non Profit
Country United Kingdom
Start 03/2009 
End 04/2014
 
Title Human embryonic stem cell lines with clinically relevant mutations 
Description The sixteen lines of stem cells on the NIH Registry carry genes for various hereditary disorders including Duchenne Muscular Dystrophy, Huntington's disease, cystic fibrosis, and rarer conditions such as Von Hippel-Lindau Syndrome, Wiskott-Aldrich syndrome, spinal muscular atrophy, myotonic dystrophy and neurofibromatosis. 
Type Of Material Cell line 
Provided To Others? No  
Impact Sixteen of human embryonic stem (hES) cell lines derived at King's have been approved by the US National Institutes of Health (NIH) and placed on their Stem Cell Registry, making them freely available for federally-funded research in the USA. King's is now one of the five biggest providers of disease-specific human embryonic stem cells lines on the NIH Registry, and the largest from the UK. The development is a significant milestone for King's and keeps the university at the forefront of global research into regenerative medicine. 
URL http://grants.nih.gov/stem_cells/registry/current.htm
 
Title Human embryonic stem cell lines with clinically relevant mutations 
Description We have so far derived 22 lines carrying clinically relevant genetic mutations derived from affected embryos following preimplantation genetic diagnosis (PGD) (HFEA licence R0075) which includes cystic fibrosis (4 lines), Huntington's disease (7 lines), myotonic dystrophy type 1 (1 line), neurofibromatosis type 1 (2 lines), spinal muscular atrophy type 1 (1 line), Von Hippel-Lindau cancer syndrome (3 lines), ß-thalassemia (2 line), Wiskott-Aldrich syndrome and cystic fibrosis carrer (1 line), and Turner syndrome (1 line). 
Type Of Material Cell line 
Year Produced 2013 
Provided To Others? Yes  
Impact The cells are or will be deposited in the UK Stem Cell Bank. The deposition process is ongoing. The cell lines will be then be available to other researchers. The cell lines are also sumnitted to NIH Registry 
URL http://www.kcl.ac.uk/medicine/research/divisions/wh/groups/medicine/hescell.aspx
 
Title Reseearch grade normal hES cel lines 
Description We have derived 9 lines from normal embryos cryopreserved in-house or from one of the ten collaborating IVF units (HFEA licence R0133). 
Type Of Material Cell line 
Year Produced 2007 
Provided To Others? Yes  
Impact The cell lines are either submitted or in process of submission to UKSCB. They will be available to researchers worldwide. 
 
Description Biochemical Engineering 
Organisation University College London
Department Biochemical Engineering
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaboration with Regenerative Medicine group
Collaborator Contribution Knowledge transfer and experience
Impact Publications: 17465755 17635044 PhD student completed thesis http://eprints.ucl.ac.uk/18592/1/18592.pdf
Start Year 2006
 
Description hESCCO (Human Embryonic Stem Cell Coordinators) 
Organisation Saint Mary's Hospital, Manchester
Department Department of Obstetrics and Gynaecology
Country United Kingdom 
Sector Hospitals 
PI Contribution The hESCCO group was formed before this grant was approved. Therefore any collaborations made had already been established. With regard to this, we organised group meetings and established lines of communication between parties.
Collaborator Contribution Knowledge transfer and experience.Knowledge transfer and experience
Impact A group patient information and consent form has been produced in the past to give patients uniform information. The group has established a website in which to communicate. We have also produced a joint publication - Ref 18154466.
 
Description hESCCO (Human Embryonic Stem Cell Coordinators) 
Organisation Sheffield Teaching Hospitals NHS Foundation Trust
Department Assisted Conception Unit
Country United Kingdom 
Sector Hospitals 
PI Contribution The hESCCO group was formed before this grant was approved. Therefore any collaborations made had already been established. With regard to this, we organised group meetings and established lines of communication between parties.
Collaborator Contribution Knowledge transfer and experience.Knowledge transfer and experience
Impact A group patient information and consent form has been produced in the past to give patients uniform information. The group has established a website in which to communicate. We have also produced a joint publication - Ref 18154466.
 
Description hESReg European Stem Cell Registry 
Organisation European Commission
Department EC FP6 Collaborative Projects
Country European Union (EU) 
Sector Academic/University 
PI Contribution Member of Scientific Advisory board and contributor to Bank registry
Collaborator Contribution Contribute to data in registry Braude is member of scientific advisory committee
Impact First European wide stem cell registry of Embryonic and iPS stem cells http://www.hescreg.eu/
Start Year 2007
 
Description Brazilian Association for Stem Cell Therapy Meeting 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact More than 200 people attended the talk

The presentation was followed with 15 minute Q+A session. Multiple questions form peers as well as from graduate students in audience
Year(s) Of Engagement Activity 2013
URL http://www.abtcel2013.bio.br
 
Description Clinical embryologist meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Primary Audience Public/other audiences
Results and Impact ACE meeting Edinburgh (Jan 09). "Implications of donating embryos for stem cell research"

None
Year(s) Of Engagement Activity 2009
 
Description DKF Research Conference, Bern, Switzerland 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? Yes
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact More than 100 academic researchers attanded the lecture

Intense Q&A session lasting more than 30 minutes
Year(s) Of Engagement Activity 2012
 
Description Embryologist national meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact Jan 09 - "Implications of donating embryos for stem cell research, ACE meeting, Edinburgh

Information for UK embryologists about stem cell research; need, and practical and ethical implications
Year(s) Of Engagement Activity 2009
 
Description Infertility nurses meeting 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact Glenda Cornwell Sept 07 - "Embryonic Stem Cell Research: The nurses role" National Fertility Nurse annual conference

Informing nurses involved in assisted conception units about need and use of surplus embryos for stem cell research
Year(s) Of Engagement Activity 2007
 
Description Lecture to Tissue bankers 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact Glenda Cornwell Apr 07 - "Embryonic stem cell donation: The hESCCO experience" British Association for Tissue Banking

Information to general tissue banking audience about recruiting donors to embryonic stem cell reserach Published abstract Abstracts from the Annual Scientific Meeting of the British Association for tissue banking
Year(s) Of Engagement Activity 2007
 
Description Seminar - London 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Primary Audience Health professionals
Results and Impact Presented update of research results to embryologists and research nurses from collaborating units

Continuing acquisition of research embryos from collaborating units
Year(s) Of Engagement Activity 2009,2010,2011
 
Description Stem cells and regenerative medicine seminars, Ljubljana, Slovenia 
Form Of Engagement Activity A talk or presentation
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Undergraduate students
Results and Impact About 30 undergraduate students and 10 faculties attanded a series of 6 lectures on stem cells and regeneratiev medicine

University of Ljubljana, Faculty of Pharmacy is currently applying for a Public Tender for cofinancing activities in years 2012-15, which stimulate openness of Slovenian Higher education into international environment released by Ministry of Education, Science, Culture and Sport - financed by the European Union and the Republic of Slovenia.

D Ilic has been invited to participate as a guest expert and leader of international Workshop in Stem cells and Regenerative Mediince within the proposed project if being selected at the public tender.
Year(s) Of Engagement Activity 2012
 
Description Workshop on stem cell & cancer research 
Form Of Engagement Activity A formal working group, expert panel or dialogue
Part Of Official Scheme? No
Type Of Presentation Keynote/Invited Speaker
Geographic Reach International
Primary Audience Other academic audiences (collaborators, peers etc.)
Results and Impact CONFERENCE: King's College London and national Yang-Ming University, Taiwan, workshop on stem cell & cancer research
DATE: 17-19 Sep 2012
ORGANIZER: www.kcl.ac.uk
TITLE: Pluripotent stem cells at King's
AUTHORS: Dusko Ilic
LOCATION: King's College London, London, UK

networking, promotion of our research and resources
Year(s) Of Engagement Activity 2012
 
Description video clip on BBC website 
Form Of Engagement Activity A magazine, newsletter or online publication
Part Of Official Scheme? No
Geographic Reach International
Primary Audience Public/other audiences
Results and Impact SERIES: Health Explained
TITLE: How to make stem cells
DATE OF PUBLICATION: 21 Jun 2012
URL: www.bbc.co.uk/news/health-18496355

promoting our research
Year(s) Of Engagement Activity 2012