Musculoskeletal system

The musculoskeletal system comprises the anatomical structures and tissues that provide mechanical support to vertebrate organisms, and enables movement and other bodily functions such as breathing and mastication. The five tissue types specific to the musculoskeletal system are: bone, cartilage, tendon, ligament and muscle. Degeneration of any or all these tissues is associated with ageing and with several chronic diseases such as osteoarthritis (cartilage degeneration), osteoporosis (bone degeneration), desmopathy (cruciate ligament rupture), tendinopathy (Achilles tendinopathy) and muscular dystrophy (muscle wasting).

Our aim is to better understand the molecular mechanisms causing tissue degeneration in the musculoskeletal system and to use stem cells and tissue engineering to reconstruct damaged tissue, alleviate pain and improve the quality of life of patients and elderly people.

Our research focuses on the following areas of the musculoskeletal system but includes integrated approaches to characterise musculoskeletal stem cells and to understand the musculoskeletal system as a whole:

Cartilage: Osteoarthritis is a degenerative disease of the articulating joints that leads to a loss of cartilage and changes to the underlying bone. Early restoration of cartilage function by replacement of the damaged tissue with new cartilage engineered in the laboratory may alleviate symptoms in many patients and delay or prevent the need for joint replacement. We can tissue engineer cartilage with good biochemical and histological properties using bone marrow-derived mesenchymal stem cells, even if these cells are isolated from elderly patients with advanced osteoarthritis. Using this cartilage produced in the laboratory from stem cells we can both prevent and treat osteoarthritis. Moreover, this approach makes it possible for us to consider treating patients using their own cells, so avoiding the risk of immune rejection of the engineered cartilage after it has been implanted.

Muscle: Voluntary muscles, also called skeletal muscles because of their anatomical association with the skeleton, have a remarkable growth and regenerative capacity when damaged by a trauma or in recovering from atrophy after a period of immobilisation. However, muscle loses growth and regenerative capacity with ageing or in the presence of chronic injury. We have shown that the resident muscle stem cells can be “boosted” to restore full regenerative capacity in old and dystrophic mice. We are now in the process of translating our findings from mice to humans with the aim of developing novel therapeutic strategies to treat muscle loss and muscle wasting in disease and ageing.

Tendon / Ligament: Tendons and ligaments are connective tissues that attach muscle to bone (tendon) and bone to bone (ligament). Together these tissues are responsible for stabilising joints and transmitting contractile forces of the muscle into skeletal movement. Tendons and ligaments have poor cellularity and vascularity and as a consequence have a limited capacity for self-repair leading to age and disease-related degeneration. We are comparing tendon and ligament tissue from different species (human, equine, canine, ovine) and using a combination of genomic and proteomic approaches to characterise the changes in cell physiology and tissue structure that are associated with ageing and disease, with the aim of identifying therapeutic targets that enable early diagnosis or treatment of disease. We are also combining stem cells and biomaterials in tissue-engineering strategies to repair graft tissue and enhance graft attachment following reconstructive surgeries.

Bone: Bone is a surprisingly complex tissue, and the various cells within it reside in a dynamic environment rich in stimuli such as growth factors and mechanical forces which combine to regulate its structure, strength and response to injury. We are particularly interested in how the process of bone healing is regulated by physical activity, and how the mechanical action of the skeleton helps to guide the process of bone formation through interaction with other biological processes such as growth factors and the extracellular matrix. Bone is usually capable of complete healing, but disease or traumatic injuries can impair this process and have significant healthcare implications across the population, particularly for the elderly. We are using bone marrow stem cells cultured in 3D biomaterial scaffolds to develop new therapies which aim to restore lost bone, improve healing and provide novel treatments for age-related degenerative diseases.

Our key investigators: Pete Clegg, Eithne Comerford, Anthony Hollander, Elizabeth Laird, Patricia Murray, Rachel Oldershaw, Mandy Peffers, Vanya Petrovik-Vaughan, Dada Pisconti, Simon Tew, Kasia Whysall, James Henstock.

Our cross-disciplinary collaborators: Riaz Akhtar, Philipp Antczac, Rob Beynon, Massimo Degano, Francesco Falciani, Olga Mayans, Matthew Peak, Stefan Spinty

Our funders: BBSRC, MRC, Arthritis Research UK, European Commision, Wellcome Trust.

To find out more, contact: Anthony Hollander