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Growing the field of stem cell research

Growing the field of stem cell research - 31 March 2014. Wellcome Library London
Highlights from: 20 years of bioscience

BBSRC has been a driving force behind UK stem cell research over the past 20 years, having played a key role in building research capacity through targeted funding initiatives and specialist training for researchers.

BBSRC's support for research to understand the basic biological properties and behaviour of stem cells, from both model organisms and humans, has paved the way for the emerging, inter-disciplinary field of regenerative medicine – described by the Chancellor of the Exchequer as one of 'Eight Great Technologies' in 2012.

The ability of stem cells to transform themselves into different cell types has made them a source of fascination to scientists for more than 100 years (ref 1). But it's really only over the past 20 years that the science has come of age.

The first dedicated UK institute for stem cell research (ISCR) was established by the University of Edinburgh in 2000. But its origins go back a further 10 years, having started life as the Centre for Genome Research (founded by the Agriculture and Food Research Council) with a broad remit to develop and exploit techniques in transgenic biology, such as germline manipulation, stem cell manipulation and genetic manipulation by mutagenesis, of relevance to agriculture, medicine and mammalian biology.

The Centre received core-funding from BBSRC throughout the 1990s and, under the Directorship of Professor Austin Smith, its research strategy became more focussed on stem cell biology.

Embryonic stem cell. Image: Annie Cavanagh, Wellcome Library London
Embryonic stem cell. Image: Annie Cavanagh, Wellcome Library London

The ISCR achieved early success in the identification of proteins that controlled the ability of embryonic stem cells to replicate limitlessly, as well as identifying a signalling pathway that promoted stem cell multiplication. The findings were useful in understanding how the fate of stem cells could be influenced.

At the same time and, by coincidence, in the same city, scientists at the BBSRC-supported Roslin Institute were studying nuclear transfer in sheep. The subsequent birth of Dolly provided the first demonstration that all the programming needed to transform a fertilised egg into a living, breathing animal was contained within a somatic cell – any cell in the body, other than sex cells or stem cells.

But, despite such rapid advances in cell technologies, there were major technical hurdles that needed to be overcome in order to realise the full potential of stem cells and to facilitate their safe application in healthcare.

Building capacity

In 1999, BBSRC launched a £2M 'gene technologies underpinning healthcare' initiative, to promote basic cell and molecular biology around gene therapy, stem cells and nuclear transfer. As well as generating high quality science and valuable intellectual property, the initiative was successful in forming a networked community of researchers ready to develop collaborative research with medical researchers and bio-medical companies.

In 2002, the UK Government announced the provision of £40M to five Research Councils under the Spending Review (SR2002) to support research on stem cells. BBSRC's share of this funding was £10.65M, of which £0.65M was used to contribute towards the funding of the UK Stem Cell Bank (see banking on quality) with the Medical Research Council (MRC). BBSRC's remaining £10M was earmarked for a 'stem cell science and engineering' initiative. This initiative ran from 2003 until 2009, split between two funding calls. The second call sought more formal cross-discipline collaborations, with 25% of these projects funded by the Engineering and Physical Sciences Research Council (EPSRC).

Banking on quality

The UK Stem Cell Bank was a world first when it opened in 2004, funded by the MRC and BBSRC. It has played an important role in developing and maintaining standards in the UK ever since and is now a significant component of the UK regenerative medicine landscape.

The Bank was established to ensure that UK research using human embryonic stem cells was ethically robust as well as to provide a repository of each and every human embryonic, foetal and adult stem cell line derived in the UK.

Today, the Bank provides quality controlled stocks of these cells that researchers worldwide can rely on to facilitate high quality and standardised research. It also prepares stocks of EUTCD-Grade cell lines for use as starting materials for the development of cellular therapies.

In the 2005 Budget, the Government announced a high level review, led by Sir John Pattison, to formulate a 10-year vision for UK stem cell research, creating a platform for coordinated public and private funding of research. Known as the UK Stem Cell Initiative, it included representatives from BBSRC, MRC, the Department for Trade and Industry, the Department of Health, the Wellcome Trust, and the private-sector led UK Stem Cell Foundation.

Pattison's 118-page report made 11 fully-costed recommendations, which were subsequently accepted by Government. Recommendation 1 was to establish a public-private partnership to explore the potential of using stem cell derived cell cultures, such as liver and heart cells, in the early, high-throughput toxicology screening of potential new medicines. The consortium, Stem Cells for Safer Medicines, represented the first significant investment by 'big pharma' in UK stem cell research. AstraZeneca, GlaxoSmithKline and Hoffman-La Roche were founding members along with the Department of Health, the Department for Innovation, Universities and Skills (now Business, Innovation and Skills), the Scottish Government, BBSRC and MRC. It was co-ordinated by the Technology Strategy Board.

University of Bath scientists have developed a more simple process to create precursor liver cells, allowing the scale on which they can be created to be increased. Image: University of Bath
University of Bath scientists have developed a more simple process to create precursor liver cells, allowing the scale on which they can be created to be increased. Image: University of Bath

Recommendation 10 stated that 'the Government should allocate additional funding to establish a UK stem cell cooperative, to maximise the cross-fertilisation between those involved in the sub-disciplines of UK stem cell research'. The resulting UK National Stem Cell Network (UKNSCN) was launched formally in 2007, hosted by BBSRC and funded by BBRSC, MRC, EPSRC and the Economic and Social Research Council. The Network made significant progress in bringing together the wide range of disciplines and interests in the UK stem cell community, most notably through its annual science meeting.

Maintaining consensus

In 2007, BBSRC and the MRC started the UK's biggest ever public consultation on stem cell research, funded by the UK Government's Sciencewise scheme. The project captured the opinion, aspirations and ambitions of 200 members of the public on the science and ethics of stem cell research, as well as canvassing the views of nearly 50 stakeholders from fields such as science, medicine, industry, ethics and religion.

The dialogue revealed that both professionals and the public valued investment in basic research that could, for instance, address obstacles to the development of treatments. But their support for translating research into treatments was conditional on ensuring that public funding was focused on 'serious' medical conditions rather than cosmetic uses.

Early applications and impact

There have been some notable demonstrations of stem cell research feeding into treatments – such as the first tissue-engineered trachea transplant in 2008, which used a technique for growing cells pioneered by BBSRC-funded research by Professor Anthony Hollander at the University of Bristol.

BBSRC-funded stem cell research has also led to the formation of several spinout companies. These include:

Future platforms

In 2012, three UK Research Councils announced their intentions to invest £25M in research to address the scientific and technical challenges required to support the development of regenerative medicine therapies for a range of applications. The UK Regenerative Medicine Platform (UKRMP) is funded by BBSRC, EPSRC and MRC.

Image: Wellcome Library London
Image: Wellcome Library London

As part of the UKRMP, £4.5M was allocated to establish a new 'hub' for pluripotent stem cell research. The Pluripotent Stem Cell Platform, directed by BBSRC-funded researcher Professor Peter Andrews, brings together a multidisciplinary team from the Centre for Stem Cell Biology, Sheffield University, the Wellcome Trust/MRC Stem Cell Institute, University of Cambridge, the Loughborough University-led EPSRC Centre for Innovative Manufacturing in Regenerative Medicine, the Wellcome Trust Sanger Institute, the BBSRC-supported Babraham Institute and the National Institute of Biological Standards and Control.

Induced pluripotent stem cell (IPSC) technology – a way of restoring the flexibility of embryonic cells (which can turn into any type of cell) to adult stem cells – is a particularly exciting area that provides the opportunity not only to develop therapies matched to a patient's own cells but also to establish more accurate cellular models of diverse human diseases based upon the genotype of affected individuals.

The continuing refinement of methodologies to achieve cell reprogramming in the production of IPSCs, for example through a better understanding of epigenetic memory – an area where BBSRC-funded researchers are world leading – could open up further applications and therapeutic options.

Milestones

  • 1968: First bone marrow transplants
  • 1978: Stem cells discovered in human cord blood
  • 1981: First in vitro stem cell line developed from mice
  • 1988: Embryonic stem cell lines created from a hamster
  • 1995: First embryonic stem cell line derived from a primate
  • 1996: Dolly the sheep is born at the BBSRC-supported Roslin Institute 
  • 1997: Leukaemia origin found as a haematopoietic stem cell, indicating possible proof of cancer stem cells
  • 1998: First human embryonic stem cell lines produced
  • 1999 and 2000: Discovery that adult mouse tissues could be manipulated to produce different cell types
  • 2000: First UK Stem Cell Research Institute
  • 2003: Proteins called Oct-4, Sox-2 and Nanog shown to be essential for stem cells to retain their ability to turn into almost any cell type and to self-renew. This research was part-funded by BBSRC
  • 2004: UK Stem cell bank opens, funded by BBSRC and MRC
  • 2006: Adult mouse cells reprogrammed to generate embryonic-like cells
  • 2007: First human induced pluripotent stem cells
  • 2007: UKNSCN launched, hosted by BBSRC
  • 2007: Stem Cell Dialogue launched by BBSRC and MRC
Image: Wellcome Library London
Image: Wellcome Library London

References

  1. www.ipscell.com/2012/04/who-really-discovered-stem-cells-the-history-you-need-to-know/