Centre Regeneratif Medicine

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                                                                          Director: Professor Sir Ian Wilmut, OBE, BSc,
                                                                          FRS, FRSE, Professor of Reproductive Science

             CCNS WAS         The MRC Centre for Regenerative Medicine (MRC-CRM) was
       ESTABLISHED IN         established in 2008 and is one of the largest centres in Europe
            FUNDAMENTAL       working on regenerative medicine. The Centre brings together basic
    2005 TO PROMOTE
 UNDERSTANDING OF STEM        stem cell research with established clinical excellence to deliver a
     RESEARCHUSE THE          “bench-to-bedside” approach aimed at developing new treatments
  KNOWLEDGE TO IMPROVE        for major diseases like leukaemia, multiple sclerosis, Parkinson’s
         COGNITION, TO
   HUMAN HEALTH, ANDAS        disease, motor neuron disease and chronic liver disease.
         IT APPLIED TO
   PROVIDE LEADERSHIP IN      Currently operating across two sites, Little France and King’s
              MEDICINE,       Buildings, the Centre will relocate in 2011 to a state-of-the-art,
GENERATION OF BASIC AND       purpose built research facility currently under construction on the
   CLINICAL SCIENTISTS IN     Little France site, adjacent the Medical School, the Queen’s Medical
  STEM CELL BIOLOGY AND       Research Institute, the Royal Infirmary and linked commercial
 REGENERATIVE MEDICINE.       investment premises. With this new facility, the Centre will be ideally
                              placed to make important contributions to both basic and translational
                              aspects of developing treatments, through the combination of our
                              research in stem cell biology and being in proximity to hospital clinics
                              and other world class research centres.
 RESEARCH PROFILE                                                         MAJOR RESEARCH SUCCESSES
 Research at the MRC-CRM is structured in themes (understanding           The MRC-CRM has a strong track record in the identification and
 stem cells and their niches, technology development, and stem cells      characterisation of defined tissue progenitor/stem cell populations.
 and regenerative therapies) and body systems (currently brain and        Our strategy has been to 1) identify progenitor cells in organ/tissue
 spinal cord, blood, liver and bone and cartilage). Together, these       development via lineage analyses, 2) identify markers for these cells,
 themes and systems create an integrated matrix that allows for as        3) prospectively purify candidate cell populations, 4) to characterise
 much cross-over between researchers of different disciplines as          these populations via functional assays and 5) to exhaustively
 possible. These themes and body systems have been chosen                 phenotype the cells via expression profiling.

 because of Edinburgh’s research strengths and their tractability to      Using this general approach, our researchers have made major key
 new technologies. To further advance the research and the                contributions to the field of stem cell research and regenerative
 development of new therapies, the Centre will continue to develop        medicine. Recent contributions include the development of stem
 research technologies and will provide an in-house translational unit    cells from human skin cells without the need to use viruses in the
 for cell culture at GMP standard.                                        process (Kaji et al, Nature, 2009), the discovery of a source of adult
                                                                          haematopoietic cells in the embryo (Dzierzak and Medvinsky,
 Close collaborations with the adjacent Centres for
                                                                          Development, 2008), the development and improvement of a novel
 Neuroregeneration (Director Prof P Brophy), Reproductive Biology         method to generate extensive haematopoietic stem cells
 (Director Prof P Saunders), Cardiovascular Research (Director Prof B     (Liakhovitskaia et al, Stem Cells, 2009; Taoudi et al, Cell Stem Cell,
 Walker), the Euan MacDonald Centre for MND Research (Director            2008; Medvinsky et al, Current Protocols in Stem Cell Biology, 2008;
 Prof S Chandran) and the Eye Pavilion will support additional work in    Yang et al, Journal of Immunological Methods, 2008), understanding
 reproductive organ, endothelial and corneal repair. The current          the process of (re)myelination in the central nervous system (Camera
 interests within the MRC-CRM also provide a basis for the                et al, Journal of Cell Biology, 2009; Bauer et al, Glia, 2009; Franklin
 understanding of cancer stem cells, and this area is targeted for        and ffrench-Constant, Nature Reviews Neuroscience, 2008),
 substantial development through strategic links with the Edinburgh       understanding the abnormalities of cortical development in the brain
 Cancer Research Centre (Director Prof M Frame) and the MRC               (Marthiens and ffrench-Constant, EMBO Reports, 2009),
 Institute of Genetics and Molecular Medicine (Director Prof N Hastie).   understanding the foundations of pluripotency in embryonic stem
                                                                          cells (Chambers and Tomlinson, Development, 2009), the
                                                                          development of a method for the differentiation of mouse embryonic
                                                                          stem cells to anterior definitive endoderm, a unique multipotent
                                                                          precursor of liver and pancreas cells (Livigni et al, Current Protocols
                                                                          in Stem Cell Biology, 2009), the development of an alternative
                                                                          strategy to generate normal human embryonic stem cell lines from
                                                                     VALUE ADDED
clinically failed eggs (De Sousa et al, Stem Cell Research, 2009),
and the development of a strategy to overcome problems with the      Based on comparison with other national centres, the
differentiation of embryonic stem cells into functional hepatic or   MRC-CRM will occupy a unique position within the UK. It is
pancreatic cells (Morrison et al, Cell Stem Cell, 2008).             currently the only Centre in the UK that will bring together
                                                                     into a single building basic and clinical stem cell scientists
                                                                     working on regeneration, and is also one of the largest in
                                                                     the world to do so. It is the largest UK grouping of
                                                                     researchers in this field, comprising 22 independent groups
                                                                     and approaching 150 research staff. Additionally the
                                                                     MRC-CRM will be physically located next to other centres
                                                                     of excellence (see below) and will be in close proximity to a
                                                                     state-of-the-art teaching hospital. These links will be vital to
                                                                     the success of stem cell therapy for solid organs, which will
                                                                     depend upon knowledge of the pathological and repair
                                                                     mechanisms within these organs.

                                                                     Key to the success of the MRC-CRM will be its location at
                                                                     the heart of the Little France Medical campus. As well as
                                                                     the Royal Infirmary of Edinburgh and the University’s
                                                                     Medical School, Little France is home to the Queen’s
                                                                     Medical Research Institute (QMRI). The £50M QMRI opened
                                                                     in 2005 and is home to 600 researchers working in three of
                                                                     the University’s most prestigious research centres: The
                                                                     Centre for Reproductive Biology, the MRC Centre for
                                                                     Inflammation Research (CIR) and the Centre for
                                                                     Cardiovascular Science (CVS). The QMRI has already
                                                                     become a magnet for top quality scientific recruitment, with
                                                                     scientists attracted by the possibilities of both horizontal
                                                                     and vertical collaborations between the three centres. The
                                                                     MRC-CRM has therefore developed strategic partnerships
                                                                     with complementary disciplines with some of its PIs having
                                                                     joint appointments in the research centres in the QMRI.

                                                                     MAJOR SOURCES OF FUNDING
                                                                     MRC, Wellcome Trust, LFR, BBSRC, JDRF, Scottish
                                                                     Enterprise, SFC, Stem Cell Foundation, Geron Corp.


RESEARCH GROUPS                                                          MAJOR FACILITIES/EQUIPMENT
Director: Prof Sir Ian Wilmut, Chair of Reproductive Biology             The MRC-CRM already has high quality in-house facilities for basic
                                                                         research on both the Little France and King’s Buildings sites. In
Deputy Director: Prof Charles ffrench-Constant, Chair of MS
                                                                         addition, there is a high level of infrastructure support.
Programme co-ordinators: Theme co-ordinators: Pluripotency and           • A state-of-the-art centralised facility for isolation and culture of
                                                                           both human and mouse embryo stem cells, managed by a
iPS (Dr Ian Chambers), Lineage and Cell Specification (Prof Claus
                                                                           dedicated tissue culture manager and supported by two part-time
Nerlov), Neural Differentiation and Tissue Repair (Prof Charles
                                                                           technical staff, ensures a uniformly high standard of lab technique
ffrench-Constant), Haematopoietic Stem Cell Biology and
                                                                           and reagents across the Centre.
Regeneration (Prof Alexaner Medvinsky), Liver Stem Cell Biology and
Tissue Repair (Prof Stuart Forbes). To promote collaboration within      • A transgenic facility covering provision of mouse ES cells,
the Centre, we adopt a flexible approach to these themes with each         blastocyst injection, derivation of custom mouse ES cell lines and
PI having one or more secondary affiliations. We also invest in            other embryo micromanipulations, managed by a highly skilled
technological development in all areas.                                    and experienced manager and supported by a skilled technician,
                                                                           streamlines production of genetically modified ES cell and mouse
Principal Investigators: Dr Pierre O Bagnaninchi (cell and tissue
monitoring), Dr Clare Blackburn (thymus development and
regeneration), Dr Josh Brickman (embryonic patterning), Dr Ian           • Flow cytometry is available as an operator-run in-house service,
Chambers (embryonic stem cell biology), Dr Siddarthan Chandran             comprising a Cytomation MoFlo that permits high speed sorting in
(stem cells and regenerative neurology), Dr Paul A De Sousa                up to 4 colours (6 parameters), including true UV, a
(pluripotent cell translation), Prof Charles ffrench-Constant              Becton-Dickinson FacsCalibur (6 parameter, 4 colour) and a
(myelination and repair in the central nervous system), Prof Stuart        Dako-Cytomation Cyan (8 parameter 6 colour).
J Forbes (liver stem cells and regeneration), Dr Lesley Forrester        • Imaging facilities include two Leica AOBS confocal microscopes
(mesoderm and haematopoietic differentiation), Dr David Hay                (upright and inverted), with an environmentally controlled chamber
(human embryonic stem cell hepatocyte development), Prof John              for time-lapse analysis; a Nikon microscope with time lapse
Iredale (tissue fibrosis), Dr Keisuke Kaji (biology of reprogramming),     imaging capability including gassed temperature controlled
Dr Tilo Kunath (early embryonic lineages), Dr Sally Lowell (embryonic      electronic multi-well monitoring; a wide selection of conventional
stem cell differentiation), Prof Alexander Medvinsky (ontogeny of          inverted microscopes with Improvisation Open Lab image
haematopoietic stem cells), Prof Claus Nerlov (tissue stem cell            capture/manipulation work stations; a camera lucida digital
genetics), Prof Anura Rambukkana (adult tissue cell plasticity,            imaging station; as well as upright, inverted and dissecting
reprogramming and regeneration), Prof Jim Ross (tissue injury and          microscopes with various fluorescence optics, photo-attachments
repair), Dr Andrew Smith (genome engineering), Dr Simon Tomlinson          and video monitors. Additionally we have access to atomic force
(stem cell bioinformatics), Dr Paul Travers (immune modulation and         microscopy via a Veeco Bioscope with fluorescent imaging, a
regeneration), Prof Marc L Turner (SNBTS cellular therapy group),          Skyscan µCT-imager capable of 4µm resolution and a PALM laser
Dr Anna Williams (remyelination in multiple sclerosis), and Dr Val         capture device for single cell analysis.
Wilson (early embryo development).                                       MRC-CRM also has state-of-the-art equipment for experimental
                                                                         embryology (mouse and Xenopus); quantitative (real time) PCR;
                                                                         automated in situ hybridisation; histology; and houses facilities for
                                                                         the manufacture of solid free form bioactive devices - the production
                                                                         of these support matrices and scaffolds facilitates the incorporation
                                                                         of cells into solid structures for in vivo delivery. Centralised
                                                                         bacteriological media and glassware washing services, and SPF
                                                                         in-house animal facilities are also provided, and are all run on a full
                                                                         cost recovery basis. We have ready access to all university facilities
                                                                         on the Kings Buildings and Little France medical campuses,
                                                                         including sequencing and proteomics facilities, and fermenters for
                                                                         large scale protein production and a zebrafish facility.

                                                                         KEY EXTERNAL LINKS/COLLABORATIONS
                                                                         • RIKEN Centre for Developmental Biology, Kobe, Japan.
                                                                         • Peking University Stem Cell Research Centre, Beijing, China.
                                                                         • Harvard Stem Cell Institute, Cambridge, Massachusetts, US.
OUR NEW BUILDING                                                          STUDENTSHIP PROGRAMME
                                                                          The MRC-CRM runs a highly successful structured PhD
                                                                          programme in stem cell and regenerative medicine, aimed at both
                                                                          science and medical graduates. It provides a state-of-the-art
                                                                          theoretical background in stem cell biology, developmental biology,
                                                                          regenerative biology and stem cell genetic engineering, through
                                                                          short courses taught by basic and clinical stem cell scientists.
                                                                          In the first year, alongside these taught courses, students will
                                                                          undertake short rotation projects in basic and clinical science
                                                                          laboratories. This will be followed by a three-year main PhD
                                                                          project. Collaborative projects that provide cross-disciplinary
                                                                          experience and/or promote translation into the biotechnology or
                                                                          clinical fields are encouraged.
                                                                          We also have three-year studentships available, which are more
                                                                          suitable for candidates who wish to combine a PhD with
Architect’s image of the new Scottish Centre for Regenerative
                                                                          postgraduate medical training or have already attained M.Sc.
Medicine building, a state-of-the-art research facility which will open
in 2011.                                                                  or M.Res qualifications.
                                                                          All students have a primary supervisor, normally their research
FUTURE PLANS AND DIRECTIONS                                               group leader, and an assistant supervisor from another University
The MRC-CRM was established in 2008. Our strategic                        Department. Progress of each student is monitored by a
objectives for the next 3 years are to:                                   committee of three senior scientists.

• Merge existing internationally-competitive basic, clinical and          Students are expected to participate in structured post-graduate
  translational efforts in stem cell and regenerative medicine into a     activities, including 1) a generic and transferable skills training, 2)
  single collaborative unit at Little France.                             weekly meetings of their research group, 3) a PhD students’
                                                                          discussion club, 4) weekly internal and external seminars, and 5)
• Identify and address key knowledge gaps in basic and                    an annual PhD day.
  translational stem cell science through the development of our
  two major research platforms: 1) understanding stem cells and
  their niches, and 2) technology development.
                                                                          POSTGRADUATE SCHOLARSHIPS
                                                                          MRC, College and other scholarships.
• Develop our translational cross-platform programmes in stem
  cell research and regenerative medicine, with particular focus on
                                                                          POSTGRADUATE CONTACT DETAILS
  brain and spinal cord, blood, liver, and bone & cartilage. These
                                                                          Mrs Pat Hope, Postgraduate Secretary, MRC Centre for
  areas have been chosen because of Edinburgh’s globally-
                                                                          Regenerative Medicine, Roger Land Building, King’s
  leading strengths and their tractability to the new technologies.
                                                                          Buildings. Telephone 0131 650 5828, email
  Within each programme, our principal aims are to: 1) provide
  increased understanding of the properties of stem cells, 2)
  develop protocols to allow in vitro production and expansion of
  defined human cell and tissue products, 3) use these cells in
  drug discovery, 4) test these drugs and cells in vivo in
  pre-clinical models and 5) test these products for safety and
  efficacy in the clinic.
• Establish a training pipeline for basic scientists and clinicians         CONTACT DETAILS
  at all career levels to support the critically needed expansion in
  the field.                                                                MRC Centre for Regenerative Medicine
                                                                            Chancellor’s Building
• Develop collaborative research programmes with small and
  medium sized enterprises and pharmaceutical companies.                    49 Little France Crescent
                                                                            Edinburgh EH16 4SB
• Create a centre for proactive engagement with the public
  and media to inform and advance the important and highly
                                                                            Telephone 0131 242 6630
  topical ethical, legal and social debates around stem cell

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