ISTM

ISTM Research theme: 1. Bioengineering & Therapeutics

Areas of Interest:

• Study of the intervertebral disc in health and pathology.
• Understanding factors which can lead to disc cell death and dysfunction.
• Identifying pathological pathways leading to disc degeneration, including study of inflammatory mediators which may be released from prolapsed intervertebral discs and degradative enzymes.
• Determining factors which could control nerve growth into intervertebral discs.
• Developing cell based treatments for disc degeneration.
• Developing injectable nuclear replacements for patients with disc degeneration and back pain.
• Monitoring the quality of repair tissue in cell based therapies of articular cartilage and attempting to establish standardised international assessment criteria.
• Studying the production and expression of extracellular matrix components in ACI-treated patients.
• Identifying biomarkers of cartilage degeneration for OA and discogenic Back pain patients.

Centre for Spinal Studies:

Research work on-going in the Centre for Spinal Studies within the Robert Jones and Agnes Hunt Orthopaedic Hospital addresses 2 main clinical areas:  Spinal Disorders (Clinical lead: Mr J Trivedi), including back pain and deformities, and Spinal Injuries (Clinical lead: Mr W El Masri).

Several ISTM personnel are based here including Professor Sally Roberts, Director of Spinal Research and Dr Eustace Johnson who leads the Spinal Injury research.  Dr Simon Stephan is working here on a BBSRC funded grant and several post-graduate students, including Karina Wright, Philip Jones, Stefan Bajada, Merlin Walter and Irenka Mazakova. 

The Centre for Spinal Studies, Oswestry.

Karina is working on identifying the mechanisms involved in bone marrow stromal cell (MSC) derived nerve growth, as many studies have shown that MSC transplantation may provide therapeutic benefits to people with spinal cord injury.  Phil is studying proteins associated with calcification of cartilages, in both normal and pathological situations.  Stefan is interested in non-union bone fractures, ie fractures which do not heal even after several different treatments. He is focusing on the isolation and characterisation of MSC from the non-union region in affected patients, to provide a better understanding of the biology which should lead to improved therapeutic options. Stefan is also trial manager for the first clinical trial of autologous expanded MSCs in the treatment of non-union.
Irena is studying the extracellular matrix molecules and their influence on innervation and vascularisation in the osteochondral tissue.  This study is part of the EU funded MyJoint project (www.myjoint.org) which has the aim of creating a tissue engineered biological joint for patients with dysfunctional or damaged joints.  Merlin is working on the development of cell transplantation and tissue engineering techniques for the treatment of pressure ulcers in skin.

In addition, within the Centre are several other researchers involved in related topics.  Funding has been from many sources, including EPRSC, BBSRC, EU, the Institute of Orthopaedics Oswestry and several Medical Research Charities including the Arthritis Research Campaign.

Selection of Publications

• Bhosale AM, Myint P, Roberts S, Menage J, Harrison P, Ashton B, Smith T, McCall I, Richardson JB. (2007) Combined autologous chondrocyte implantation and allogeneic meniscus transplantation: A biological knee replacement. The Knee 14:361-8
• Johnson WEB, Roberts S. (2007) “Rumours Of My Death May Have Been Grossly Exaggerated”: A Brief Review Of Cell Death In Human Intervertebral Disc Disease And Implications For Cell Transplantation Therapy.  Biochem Soc Trans 35: 680-682.
• Knutsen G, Drogset JO, Engebretsen L, Grantvedt T, Isaksen V, Ludvigsen TC, Roberts S,  Solheim E, Strand T, & Johansen O (2007) A Randomized Trial Of Aci Versus Microfracture. The Picture At Five Years.  J Bone Joint Surg (Am) In Press
• Wright K, El Masri W, Osman A; Roberts S; Chamberlain G; Ashton B Johnson WEB (2007), Bone Marrow Stromal Cells Stimulate Neurite Outgrowth Over Neural Proteoglycans (CSPG), Myelin Associated Glycoprotein and Nogo-A.  Biochem. Biophys. Res. Comm. 354: 559-566
• Yu J; Fairbank JCT; Roberts S & Urban JPG (2007) Microfibrils, elastin fibres and collagen in the Intervertebral Discs of young normal human and bovine tails. J Anat 210:460-471
• Balain B, Eisenstein SM, Alo GO, Darby AJ, Cassar-Pullicino V, Roberts S, Jaffray DC.  (2006) Coccygectomy For Coccydynia: Case Series And Review Of Literature. Spine 31:E414-20.
• Roberts S, Evans EH, Kletsas D, Jaffray Dc & Eisenstein SM (2006) Senescence in Human Intervertebral Discs Eur Spine J (2006)15 Suppl 3S312-6.
• Johnson WEB, Wootton A, El Haj A, Eisenstein SM, Curtis ASG & Roberts S. (2006) Topographical Guidance of Intervertebral Disc Cell Growth In Vitro: Towards the Development of Tissue Repair Strategies for The Anulus Fibrosus. Eur Spine J (2006)15 Suppl 3S389-96.
• Sivan S, Tsitron E, Wachtel E, Roughley PJ, Sakkee N, Van Der Ham F, Degroot J, Roberts S, Maroudas A. (2006) Aggrecan turnover in human intervertebral disc as determined by the racemization of aspartic acid. JBC 281:13009-14
• Roberts S, Menage J, Trivedi J, Evans EH (2006) Histology and Pathology of the Human Intervertebral Disc.  J Bone & Joint Surg (Am):88A(Suppl 2):10-14
•  E, Sivan S, Wright KT, Eisenstein SM, Maroudas A, Roberts S. (2006) Human intervertebral disc cells promote nerve growth over substrata of human intervertebral disc aggrecan. Spine 31:1187-93.
• Akimau P, Bhosale A, Harrison PE, Roberts S, Mccall IW, Richardson JB, Ashton B (2006) Autologous chondrocyte implantation with bone grafting for osteochondral defect due to posttraumatic osteonecrosis of the hip – a case report.  Acta Orthop Scand 77:333-336
• Johnson WEB, Caterson B, Eisenstein SM & Roberts S. (2005) Human Intervertebral Disc Aggrecan Inhibits Endothelial Cell Adhesion and Cell Migration In Vitro. Spine 30:1139-1147.
• Yu J; Fairbank JCT; Roberts S & Urban JPG (2005) The Elastic Fibres Network of the Anulus Fibrosus of the Normal and Scoliotic Human Intervertebral Disc. Spine 16: (1815:1820).
• Roberts S, Butler RC (2005) Inflammatory mediators as potential therapeutic targets in the spine. Current Drug Targets - Inflammation and Allergy 5:89-98.
• Roberts S, Evans H, Menage J, Urban JPG, Bayliss MT, Eisenstein SM, Rugg MS, Milner CM, Griffin S & Day AJ. (2005) TNFα-stimulated gene product (TSG-6) and its binding protein, IαI, in the human intervertebral disc: new molecules for the disc. Eur Spine Journal 14:36-42.
• Whittaker J-P, Smith G, Makwana N, Roberts S, Harrison PE, Laing P & Richardson JB. (2005) Early Results of Autologous Chondrocyte Implantation in the Talus. J Bone Joint Surg 87B:179-183.
• Tins BJ, Mccall IW, Takahashi T, Cassar-Pullicino V, Roberts S, Ashton B & Richardson J (2004) Autologous Chondrocyte Implantation in Knee Joint: MR Imaging and Histologic Features at 1-Year Follow-up. Radiology 234:501-508.
• Knutsen G, Isaksen V, Engebretsen L, Ludvigsen TC, Drogset JO, Grøntve T, Solheim E, Strand T, Roberts S & Johansen O. (2004)  A randomized trial of autologous chondrocyte implantation versus microfracture in the knee.  J Bone Joint Surg 86A: 455-464.
• Roberts S, McCall, IW, Darby, AJ, Menage, J, Evans, EH, Harrison PE, RI Chardson, JB (2003) Autologous chondrocyte implantation for cartilage repair: monitoring its success by magnetic resonance imaging and histology. Arthritis Research and Therapy 5, pp60-74.