In vitro cartilage tissue engineering to model arthritis
Researchers within the Matrix Biology & Tissue Repair Research Unit have developed a human 3D cartilage model engineered from stem cells. This model is unique in that it faithfully recapitulates articular cartilage architecture and gene expression profiles, as well as tissue responses, and we can now apply different stimuli to trigger pathological processes that mimick joint disease, such as osteoarthritis.
Osteoarthritis is the most common musculoskeletal disease, affecting over 40% of people aged 65, and currently over 8 million adults in the UK alone. This chronic, progressive joint disorder causes pain and loss of mobility, yet there is currently no effective therapy beyond pain management, improved nutrition or exercise and ultimately surgical joint replacement.
The 21st Century osteoarthritis challenge requires new approaches to accelerate development of effective treatments, i.e. treatments that can modify the disease course when given at an early stage. A step in this direction is the development of an artificial human synovial joint to facilitate rapid drug screening. Currently, this relies heavily on animal models, which is inefficient, ethically problematic and expensive, and produced drugs failing in clinical trials due to off-target side effects or failure to predict human disease.
This project will generate a ‘state-of-the-art’ organotypic model of a human joint by integrating other tissues and cell types with the existing articular cartilage model (e.g. synovial tissue, subchondral bone, adipose tissue and immune cells) to reproduce the interplay of tissues in health and disease processes. This model (a ‘joint on a chip’) will ultimately allow us to mimic human joint physiology, and will be tested and validated as a tool for biomarker discovery and pharmacological intervention studies.
The PhD student will employ human stem cells and iPS cell technology, along with other molecular biology and cell biology techniques as well as microfluidic technology in musculoskeletal tissue engineering. The successful applicant will join an international team of researchers in a Center of Excellence for Arthritis Research and have access to state-of-the-art technology to address research questions and long-standing expertise in research translation.
More information on the Matrix Biology & Tissue Repair Research Unit.