Medical Research Council (UK) – January 2012 Update

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The Medical Research Council (MRC) is a government-funded national organisation that promotes and supports research and postgraduate training in all areas of biomedical science. Its aims are to maintain and improve human health, and to contribute to national wealth and quality of life. For 90 years, MRC researchers have been the driving force behind a stream of remarkable advances that have transformed medicine and are benefiting people all over the world. Today, research at MRC centres, universities and hospitals throughout the UK extends from the laboratory to the bedside and beyond, and is building on past achievements to tackle the major health challenges of the 21st century.

MRC research on stem cells

The MRC is funding research aimed at making stem cell therapy a reality. Our scientists are investigating all aspects of stem cell biology in both embryonic and adult stem cells. Work on the basics of stem cells’ identity, propagation, and how they give rise to specialised cell types, will help scientists learn how to control stem cell self-renewal and differentiation in order to achieve safe, efficient, large-scale production of defined cell types. They must also develop ways of delivering stem cells and monitoring their migration within tissues and find out how to combat immune rejection. This research is still in its infancy and faces enormous challenges. The first clinical applications are not expected for five to ten years. The MRC’s involvement in stem cell research dates back to the 1970s and 1980s, when it funded pioneering work by Professor Martin Evans at the University of Cambridge. Professor Evans was among the first to develop ways to culture ES cells derived from the mouse blastocyst, the ball of cells formed after fertilisation. Since then, the UK, by developing the necessary legislative framework, has created an ideal environment to nurture research into human stem cell therapy and to become an international leader in this rapidly advancing field of science. The MRC is working to make the most of this opportunity. It has launched a national stem cell initiative, and is supporting some of the world’s top stem cell researchers. The MRC has established a new funding committee to specifically support the application of stem cell technology and the future delivery of clinical treatments using stem cells. The Translational Stem Cell Research Committee was launched in summer 2008 and meets three times a year to fund researcher-led applications submitted in response mode as well as through targeted calls for proposals.

Recent Achievements
  • Establishment of an MRC Centre for Stem Cell Biology and Regenerative Medicine in Cambridge, directed by Professor Roger Pedersen.
  • £3m awarded to three centres to derive up to 20 clinical grade embryonic stem cell lines that will be free from exposure to animal products and compliant with EU regulation. These lines will be made available to the research community through the UK Stem Cell Bank.
  • Regenerative medicine: £3.6m has been provided by MRC and Scottish Enterprise, in association with the UK Stem Cell Foundation, for two major translational projects at the MRC Centre for Regenerative Medicine at the University of Edinburgh. In partnership with Geron, these projects will undertake research on liver regeneration and to find new approaches to repairing damaged bone and cartilage.
  • £3m funding for seven awards through a call for proposals to address barriers in preclinical stem cell research.
  • 13 awards to establish platform technologies for human iPSC research.

Funding collaborations

  • MRC has committed £5m towards a joint call with the Californian Institute of Regenerative Medicine. The aim of the call is to support collaborative ‘disease teams’ to carry out translational work that will result in the filing of an IND to the US Federal Drug Administration within four years. MRC funding will support the UK component of successful applications.
  • MRC and the research charity British Heart Foundation have launched a £2.5m joint call to build capacity in cardiovascular stem cell research. The intention is to make two or three awards towards the establishment of future centers of excellence in this area.
Other initiatives
Stem Cells for Safer Medicine (SC4SM)

This not-for-profit company was established as a public-private partnership in 2008 to fund research leading to the development of stem cell technologies as a way of assessing toxicological responses to candidate drugs. Partners are BBSRC, MRC, Department of Health, Scottish Office and Technology Strategy Board from the public sector, and Astra Zeneca, GSK and Roche from the private sector. £1.2m has been awarded to a coordinated programme of pilot projects under phase I of this initiative, to establish scalable differentiation protocols for the production of functional human hepatocytes and cardiomyocytes, with a view to a much larger phase II of up to 5 years. See www.sc4sm.org

Regulation
New Legislation – Human Embryology and Fertilisation Act 2008

The Human Fertilisation and Embryology Act 2008 received Royal Assent on 13 November 2008. The Bill was in Parliament for a year, during which it was subject to much debate and scrutiny from which it benefitted greatly. The Government undertook a review of the law primarily in response to technological developments, such as new ways of creating embryos that have arisen since 1990, and changes in societal perspectives. The Act updates the curent law to ensure that it is fit for purpose in the 21st century and aims to keep the UK at the forefront of associated developments in treatment and research. The 2008 Act mainly amends the Human Fertilisation and Embryology Act 1990, and its research modifications in 2001, and maintains the previous UK position on human stem cell research. Key new provisions under the 2008 Act are to:

  • Ensure that all human embryos outside the body – whatever the process used in their generation – are subject to regulation.
  • Ensure regulation of inter-species or “human-admixed” embryos created from a combination of human and animal genetic material for research.
  • Ban sex selection of offspring for non-medical reasons. This puts into statute a ban on non-medical sex selection currently in place as a matter of HFEA policy.  Sex selection is allowed for medical reasons – for example to avoid a serious disease that affects only boys.
  • Alter the restrictions on the use of HFEA-collected data to help enable follow-up research of infertility treatment.

The text of the 2008 HFE Bill and supporting information is avaialble at: www.dh.gov.uk/en/Healthcare/Fertility/DH_080475  During the consultation stages for the HFE Bill, the UK Academy of Medical Sciences produced a report on the issues relating to research on embryos combining human and non-human material (inter-species embryos), which is available at www.acmedsci.ac.uk/p47prid51.html

Recent highlights from MRC funded research
Towards a therapy for Age-Related Macular Degeneration

Professor Pete Coffey, from University College London, has entered into collaboration with the biopharmaceutical group Pfizer to advance development of stem cell-based therapies for age-related macular degeneration (AMD). An MRC grant to Professor Coffey supported the underpinning research that led directly to his current work, while MRC also funded the derivation of the human embryonic stem cell lines at the University of Sheffield that have provided the basis for this work.

Induced Pluripotent Stem Cells
  • Researchers led by Dr Keisuke Kaji from the MRC Centre for Regenerative Medicine, at the University of Edinburgh, in collaboration with Dr Andras Nagy from the University of Toronto, have generated iPSC cells from human skin cells without needing to use viruses in the process and using genetic elements that allowed complete removal of the reprogramming genes.

Virus free induction of pluripotency and subsequent excision of reprogramming factors : Kaji K et al, Nature. 2009, 458(7239):771-5.

  • Research from Austin Smith’s group at the WT Centre for Stem Cell Research in Cambridge has demonstrated virus-free production of mouse iPS cells using a transposable element (PiggyBac) and a single reprogramming factor, Klf4. In doing so, it was discovered that the iPS cells could subsequently maintain themselves using their own Klf4 gene, once the PiggyBac element containing Klf4 had been removed. iPS cells generated in this way were used to create normal mice capable of germ-line transmission.

Klf4 reverts developmentally programmed restriction of ground state pluripotency. Guo G et al, Development 2009, 136(7):1063-9.

  • Self-renewal of embryonic stem cells:Research from the team of Professor Austin Smith in Cambridge demonstrated that extrinsic stimuli are dispensable for the derivation, propagation and pluripotency of ES cells, indicating that ES cells have an innate programme for self-replication. The delineation of minimal requirements for self-renewal now provides a defined platform for the precise description and dissection of the pluripotent state.

The ground state of embryonic stem cell self-renewal. Ying et al, Nature. 2008, 453(7194):519-23

  • Cancer sterm cells: A study led by Professor Tariq Enver from the MRC Molecular Haematology Unit confirmed for the first time the existence of cancer stem cells that cause the most common form of childhood cancer, acute lymphoblastic leukaemia (ALL).

Initiating and cancer-propagating cells in TEL-AML1-associated childhood leukemia. Hong D et al, Science 2008, 319(5861):336-9.

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