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Regenerative Medicine research within the Institute for Science & Technology in Medicine and its clinical partners has expanded to cover a range of applications including the intervertebral disc, and tendons.
In each of the areas summarised below, Keele has inter-linking themes in engineering tissues, enabling:
- improving the sourcing of cells,
- scaffold supports,
- biomechanical stimuli,
- biomagnetic cell targeting,
- bioreactor design,
- optical monitoring.
Bone is highly evolved and both in maintenance and repair is controlled by its biomechanical forces. Dr Jan Herman Kuiper studies the effect of these forces on fracture healing. These findings are applied in the clinic where fracture healing is measured through the increasing stiffness of the healing bones. These studies link into the MYJOINT project, and to Oscell where biomechanical controls are essential to success in stem cell therapy.
Cartilage is uniquely suited to cell engineering techniques. The Oscell laboratory and the team of cell biologists at Oswestry have studied over three hundred patients treated with variations of autologous chondrocyte implantation (ACI). These patients have failed to respond to a range of other methods of treatment but 80% have improved with ACI, and nearly all have continued to be improved over a period of 8 years. Prospective randomised trials are very difficult in surgery, but essential for testing the benefit of new techniques. Keele leads the long-term Autologous Chrondrocyte Transplantation / Implantation Versus Existing treatments (ACTIVE) clinical trial based at Oswestry with centres in UK and Europe, supported by the Medical Research Council, which has almost 200 patients entered with a planned 10 year follow-up.
Improving the treatment of arthritis is only possible with measurements of clinical outcome. The Outcome Centre at Oswestry has studied 5,000 hip resurfacing patients over the course of 10 years and undertakes a range of other studies of long term clinical outcome, under the direction of Prof James Richardson, and the support of the Institute of Orthopaedics.
Tendons are prone to degeneration and autologous stem cell therapies could provide solutions. These are being actively studied, together with longitudinal studies, by Prof Nicola Maffulli. The Orthopaedic Surgical Trials Unit at the University Hospital of North Staffordshire campus has completed three large randomised controlled trials in knee surgery, and has been involved in many systematic reviews of the orthopaedic literature. Gait analysis, material testing and development of new materials are performed at the Bionics Laboratory at the City General Hospital, University Hospital of North Staffordshire campus.
New projects are currently starting which combine these studies with other research in this grouping into novel materials for orthopaedic tissue engineering and biomagnetic repair strategies.
Cell Therapies in the Clinic
Autologous Chondrocyte Implantation (ACI) and Stem Cell Technology
Professor James Richardson is pioneering tissue engineering in Orthopaedics. The procedure of autologous chondrocyte implantation (ACI) for treatment of cartilage defects has been brought into clinical practice at the Robert Jones & Agnes Hunt Orthopaedic Hospital, Oswestry. The treatment involves removal of the patient’s chondrocytic cells, expansion on the hospital site in specially developed ISO9002 registered, good manufacturing practise (GMP) cell-culture facilities, re-implantation in the joint and defined rehabilitation. Over 300 patients have undergone treatment, with up to ten-year follow-up; results on the generation of functional cartilage from these procedures are now in several publications. Investigations are being carried out into the characterisation of human chondral cells from donor biopsies for use in ACI and the methodologies for assessing biomechanical function and structural quality of the repair tissue.
Autologous cell therapy with stem cells is now being used for bone repair: 20 patients with non-union fractures have been treated with their own bone marrow derived stromal cells (MSCs), selected and proliferated in the GMP facility in Oswestry. Early results are very encouraging.The photograph on the right shows Professor Richardson illustrating the human knee to staff and students at the Modelling Methods for Medical Engineering (3ME) Initiative Sandpit meeting, 2008
International Collaboration and Training
Keele University and its clinical partners at the Robert Jones & Agnes Hunt Orthopaedic Hospital and University Hospital of North Staffordshire have a long track record in collaborative research and training scientists and clinicians in the latest advances in regenerative medicine. Examples include:
As a Centre for Excellence in Tissue Engineering, Keele works with fifteen other European partners in the EXPERTISSUES Network which investigates new scaffold development for tissue engineering. This Euro 7million partnership is supported by the European Commission's Sixth Framework Programme.
Through the Doctoral Training Centre in Regenerative Medicine, Keele is one of three UK universities committed to the training of at least 50 researchers in the field through a 4 year PhD programme, with industrial sponsorship and including opportunities for laboratory placements in collaborators in the USA and Europe.
More recently Keele has led an initiative to enable long-term exchange of staff and students with Chinese laboratories at Tsinghua and Sichuan universities, through the HYANJI SCAFFOLD project, partnered Pisa University in Italy. This will enable the further development of nano-biomaterials and targeted drug delivery of direct relevance to bio-industry.
Keele also plays a key role training researchers for the future in regenerative medicine through the ALEA JACTA Early Stage Training Site, a Marie Curie research training grant for tissue engineering of connective tissues, enabling research students to spend a period of several months in the partner laboratories.
Keele and RJAH are involved in aspects of a further project taking a different approach to laboratory-based regeneration of tissues, MYJOINT, which aims to create a living bioreactor by growing replacement joints in the human back.
Keele is one of four partners in a "Longer Larger" award 2009-14 from the UK Biotechnology & Biological Sciences Research Council to combined advances in stem cell science and tissue engineering. Led by Southampton University, Keele is working with Nottingham, Imperial College and industry to create new in vitro and ex vivo models of human development translating to improved scaffolds and skeletal stem cell treatments for regenerative medicine.
Underpinning these initiatives over the last decade, an EU Concerted Action project, EUROCELL built links between ACI clinics around Europe, providing a forum for training, data collection and definition of outcome measures. A subsequent project, Biomechanical Interactions in Tissue Engineering and Surgical Repair (BITES), extended this research to generate osteochondral tissues with an emphasis on understanding the biomechanical environment and stimuli for building load bearing tissues. Highlights from this programme included research into the mechanical environment in defining appropriate bioreactors, including potential mechano-active materials which enhance localised mechanical signalling.