D olly put Scotland on the biotechnology map 10 years ago. Today, Scotland is famous for developing a stem cell industry with global potential, thanks to a combination of scientific expertise, government support, clear regulation, and the strong infrastructure of the Scottish Stem Cell Network.
More medical research is conducted per capita in Scotland than anywhere else in Europe with Edinburgh having one of the U.K.’s largest concentrations of stem cell clinical scientists and researchers.
As a fast-growing biotech cluster with strong international links, Scotland has attracted companies such as Stem Cell Sciences (SCS; www.stemcellsciences.com), Geron (www.geron.com), Cellartis (www.cellartis.com), and Invitrogen (www.invitrogen.com). “The reason we are located here is for the combination of cell biology know-how and clinical capability—the two together give Scotland a preeminence,” says Hugh Ilyine, Ph.D., vp and COO at Stem Cell Sciences.
Ken Snowden, director of the life science team at Scottish Enterprise (SE), Scotland’s inward investment organization, adds, “We work closely with the industry and research community on a wide range of stem cell projects and expect this support to continue for years to come. We have a mission to support stem cell research in the translational space.”
Accordingly, SE has a new fund of £5 million for such translational research, which is matched by the U.K. Stem Cell Foundation.
SE is also a major contributor to the new Scottish Institute for Regenerative Medicine (SCRM), headed by Professor Ian Wilmut. The £70 million initiative, to open in 2010, brings together the Centre for Regenerative Medicine (CRM), Institute of Stem Cell Research (ISCR), and scientists from the Roslin Institute and the University of Edinburgh’s Medical School. The SCRM is an integral part of the Edinburgh BioQuarter (EB), a £600 million life science cluster development.
Geron, which hopes to be one of the first companies to the clinic with human embryonic stem cells (hESCs), has set up a subsidiary, Geron Bio-Med (www.geron.co.uk), in Scotland. In 2006 Geron inked a collaboration with the CRM on preclinical safety and efficacy studies with hESC-derived hepatocytes for the treatment of liver failure and hESC-derived orthopedic cell types for musculoskeletal disorders.
The SCRM will house 220 academic researchers, a center for scale-up development and manufacture of cells, and units for commercial regenerative medicine research organizations and spinouts. Its work will range from basic mechanisms of stem cell regulation to translational research for drug discovery and stem cell therapies, focusing on bone, cartilage, liver, neural, and hematopoietic stem cells.
“If stem cells are to lead to treatments in the clinic then we need this translational work as well as the basic science,” explains Dr. Wilmut. “The center will bring in new research groups, companies, and clinical elements, all of which make it unique in Britain.”
“The new center offers fantastic technologies for understanding stem cells,” adds Brendon Noble, Ph.D., director of the musculoskeletal tissue engineering collaboration at the University of Edinburgh Medical School.
Dr. Noble is currently developing bone and cartilage replacement therapies with both hESCs and autologous-adult stem cells. His approach involves use of a bioactive scaffold to protect the cells, which helps them survive in the less-than-favorable tissue environment such as that found in an arthritic patient.
“Cartilage does not, unfortunately, repair itself so we need to create mechanically competent repair structures,” he explains. There is a huge market, and corresponding quality of life gains, for such therapies because people now want a hip replacement to keep them active longer. “Addition of cells may give a more genuine repair, and a more long-lived solution.”
Scotland has other centers of excellence in stem cells: in Dundee there is the Division of Signal Transduction Therapy, a consortium between the University and six leading pharma companies; Professor Tessa Holyoake’s group at the University of Glasgow specializes in cancer stem cells; and Professor Kevin Docherty’s team at the University of Aberdeen studies diabetes, focusing on how the body makes insulin by looking at the potential of hESC’s differentiation into pancreatic cells.
“We are interested in the extent to which we can mimic the human pancreas and recapitulate these events in culture,” he says. Although insulin-making cells have been found, fully functioning pancreatic cells have not; Docherty thinks they are five to ten years away. Nor is it clear how many cells would be needed to cure diabetes. A successful islet transplant requires more than 0.5 million islets. The equivalent in terms of pancreatic stem cells might exceed one billion cells, which highlights a key challenge of this industry: how to scale up.
Stem Cell Sciences is but one company addressing this key challenge. SCS is dedicated to the provision of stem cells and stem cell technologies for research and the clinic, and caters to clients in both pharma and biotech. The company has intellectual property (IP) on several technologies for highly purified stem cells and differentiated cells for genetic, pharmacological, and toxicological screens.
SCS is involved in EU Framework 6 and 7 programs via EuroStemCell. This, says Dr. Ilyine, has proved to be a unique collaboration for producing new IP, not seen in the U.S. “We see this as a very productive intersection between our company, academia, and industry.” The work has already led to development of a neural stem cell that can be grown in an adherent monolayer. SCS has carried out automation and scale up on these and has now licensed them out. The next stage is assay development, where the cells will provide a much-wanted model for CNS drug development. SCS also has a collaboration with Dialectica, a spinout of the University of Milan, which has led to it licensing in a differentiation technology for purification of neural stem cell populations.
High Quality hESCs
Another company in stem cell supply is Roslin Cells (www.roslincells.com), a not-for-profit company established in 2006 by Paul de Sousa, Ph.D., a former embryology team leader at the Roslin Institute (post-Dolly era) and now a principal investigator at the SCRM. Roslin Cells is focused upon derivation of research and therapeutic-grade hESCs in compliance with cGMP.
“Human ESCs are really an artifact of cell culture. They have a propensity to differentiate, which we have to control. If you modify the culture environment, the cells may adapt and undergo subtle changes, which might not be appreciated until you come to use them,” says Dr. de Sousa. Through addressing these challenges, Roslin Cells has already produced one definite cell line and has two more in the pipeline.
Meanwhile in January, ITI Life Sciences (www.itilifesciences.com) and Cellartis signed an agreement for the development of an automated process to produce large numbers of high-quality cells in a new Dundee-located facility. ITI Life Sciences is one of Scotland’s three Intermediary Technology Institutes (ITI; along with ITI Techmedia and ITI Energy).
The £9.5 million ITI Stem Cell Technologies program also involves the Universities of Dundee, Heriot-Watt, and Glasgow. “ITI Life Sciences helps to develop the life science industry within Scotland,” explains program manager Fergus McKenzie, Ph.D. “We look at the technology and research that already exists, along with what we are good at. Stem cells are therefore something that ITI wants to push forward in the marketplace.”
The program aims to render stem cells usable by general labs. At present, stem cells are difficult for even experienced cell biologists to handle and are slow to grow and divide. “We are looking at how to get hESCs growing, day in and day out, and how to automate the process to take out the human factor,” says Dr. McKenzie.
Cellartis already has all the QC that is needed to take this forward, with 30 different hESC lines in small-scale production. The company wanted to expand, so a division was relocated to Dundee. As a first step, a robot, which has not yet been used for hESCs, has been purchased for cell production. Meanwhile, a collaboration with the University of Glasgow will progress differentiation of the hESCs.
Scottish Biomedical (www.scottish-biomedical.com) has set up stem cell services to meet client demand for screening based on stem cells. Offering preclinical drug discovery services, it is currently looking at turning hESCs into neural cells and hepatocytes for development. CXR Biosciences (www.cxrbiosciences.com) specializes in toxicology and has a collaboration with Geron on developing hepatocyte-like cells for drug screening.
Angel Biotechnology, the manufacturing partner of the U.K. Department of Trade and Industry’s bioprocessing consortium for stem cell therapy, has also set up a facility in Edinburgh for GMP manufacturing of clinical trial material. Invitrogen, whose European headquarters is in Scotland, established a stem cell and regenerative medicine business unit here in 2005.
The Scottish Stem Cell Network (SSCN; www.sscn.co.uk) has the global outlook needed to develop this industry. It has strong links with similar organizations in Australia, Canada, California and is the cofounder of the International Consortium of Stem Cell Networks. “Our focus is to bring together the stakeholders in the industry—all who will be involved in translating the research to patient benefit,”explains executive director Marilyn Robertson.
The future for stem cells in Scotland looks bright, but challenges still remain. While SE has shown the Scottish Executive’s commitment to the field, the U.K. government as a whole has yet to fulfill financial promises made in its 2005 Stem Cell Initiative. Much hangs on how Phase I trials planned by companies like Geron and ReNeuron turn out, as failure to meet endpoints will surely put off investors. For the short term, marketing stem cells for drug discovery seems a worthwhile strategy. Transforming healthcare through stem cell therapy, however, may take a little longer.