Bioengineering

The Academic Unit of Musculoskeletal Disease is dedicated to understanding the basis for the Rheumatic Diseases and applying this knowledge to translational research with a view to the development of novel molecular and cellular therapies for Arthritis. One key activity of the Unit is in the area of Regenerative Medicine strategies specifically for joint repair in degenerative arthritis and in particular the aim to use cellular therapies in the early stages of arthritis to stave off or even prevent joint deterioration.

There are 3 major inter related factors that are crucial to the success of the Leeds Regenerative Medicine Proposal.

• The Clinical Arthritis Network
• The Mesenchymal stem cell (MSC)/Regenerative Medicine Group
• The Bioengineering Group

A). The Clinical Arthritis Network

A internationally renowned patient database that has as its principal aims the study of the earliest phases of arthritis. The Leeds early arthritis network (LEAP) and the closely integrated Yorkshire early arthritis Register (YEAR) allow access to a potential population of 3.8 million. This allows for the streamlined assessment of a variety of arthropathies including Rheumatoid arthritis, seronegative Spondyloarthropathy and Degenerative Arthritis.

The clinical strengths of this Unit have lead to the current development of a Musculoskeletal Institute that will closely dovetail with academic Orthopaedics and state of the art Musculoskeletal Imaging. .

B) The Mesenchymal stem cell (MSC)/Regenerative Medicine Group

The key to unravelling the potential of Regenerative Medicine strategies is to first understand the in vivo biology of adult stem cells in health and disease. The adult stem cell with the potential to regenerate joints is the mesenchymal stem cell (MSC) that is capable of generating bone, cartilage, fat, muscle, tendon and ligaments. As a prerequisite to unravelling the in vivo biology of MSCs we have for the first time succeeded in purifying these rare cells from 2 different sites- the bone marrow and the synovial fluid (Jones et al 2002, 2004). We have established a programme of work into a better understanding of the in vivo biology of MSCs in cartilage, bone, ligament and joint fat pads.

Mesenchymal stem cell function and activity is inextricably linked with the in vivo joint microenvironment and the role of homeostatic joint biomechanical stressing is thought to be crucial to MSC function. The inability to hitherto purify joint MSCs has hampered the proper study of this crucial physiological regulator of MSC activity and function.

We hope to establish a Chair of Regenerative Medicine in the near future. We are getting another post doctoral scientist and a Senior Lecturer to further study in vivo MSC biology in addition to the 5 members of the group. .

C) The Bioengineering Group

The Rheumatology group already has a successful Bioengineering group that is dedicated to the development of strategies to replace or repair degenerate of damaged ligament and cartilage. This group headed by Dr Bahaa Seedhom has developed one of the first knee joint protheses, the basic design of which has not changed in 30 years. The group have also developed the Leeds-Keio ligament that has been implanted into 600000 subjects to date. The group is currently active in the development of technology for cartilage defects repair.

It was discovered that the success of the artificial Leeds Kyoto ligament relates to the incorporation or integration of joint MSCs into the ligament matrix. Likewise joint MSCs appear to integrate into cartilage scaffold matrices.

The current research programme of the Bioengineering Division is complementary to that being undertaken by other colleagues within the Academic Unit, particularly that by Professor Denis McGoangle and Dr. Elena Jones There is mutual interest in mesenchymal cells and in the effect of mechanical stimulus in initiating processes of repair of joint tissues.

Vision for future

We envisage that the tripartite collaboration between Clinical Rhematology, MSc/Regenerative Medicine Group and Bioengineering could have major implications for translational research into the cellular therapy and specifically regenerative strategies for the Rheumatic Diseases. We will combine clinical and basic research to continue to determine the basis for the in vivo changes and we will determine the role in joint biomechanical stressing in the regulation of MSC activity, on MSC proliferation, differentiation and cell senescence.

The Bioengineering Group

Current active staff in Tissue Engineering within the Bioengineering Group:

Cartilage Repair :

• Ds. Bahaa Seedhom,
• Dr.Jonathan Lorrison (PDRF)
• Zhi Jie Lou (PDRF)
• Miss Elizabeth Neame - PhD student, commencing on 1. October 2004

Ligament Tissue Engineering

• Dr. Mostafa Raïf
• Mr. Michael Mesenger PhD student - 1 st year

The added value of Bioengineering to Regenerative Medicine Strategies

Members of the Bioengineering Team have a wealth of experience in both the biomechanics of joints, properties of joint tissues such as cartilage and ligaments, and in the mechanical design of apparatus required for sophisticated experiments involved in tissue engineering of cartilage and ligaments. The combination of skills, knowledge and experience of the members from the different groups within the Unit is formidable and, if coordinated, would be without parallel in the UK . The possibilities and potential of such a Group are considerable and very exciting.

for detail please contact Dr Bahaa Seldom.