Mesenchymal stromal cells in cartilage regeneration: defining the immunomodulatory characteristics on macrophage populations

Arthritis affects huge numbers of people in the UK, leading to pain and disability. We currently lack treatments for injury to joint cartilage and unfortunately many patients go on to develop arthritis. If we can address the cartilage injury early on, we can prevent the arthritis developing. This research seeks to understand cell behaviour in order to develop new treatments for joint cartilage injury.

The main aims and objectives of the research study.

Our aim was to understand how cells involved in cartilage healing interact and influence each other.

The objectives were to:

1. Combine human inflammatory cells commonly seen in the joint in a dish in the laboratory to understand how they interact and influence each other.
2. Understand how these inflammatory cells influence human cartilage cells using the same approaches. 

How this research is going to help address MSK health.

By understanding the cell behaviour, we anticipate these findings will help us develop a new biological treatment for early cartilage injury.

The main research methods, or datasets being used.

This project used human cartilage cells and other human inflammatory cells grown alone and together in a dish in order to understand how these cell types interact and influence each other. Techniques used included cell culture (growing cells in dishes), and assessing which genes the cells are expressing to understand their behaviour as well as understanding the proteins that are on the surface of cells. We also used microscopes to visualise the cells by adding fluorescent markers to see certain structures within the cells. This way we could see their shape and how they relate to each other in different environments.

Research results generated.

We have found that different types of inflammatory cells do have an impact on cartilage cells. They can influence whether the cartilage cells behave more like cells we see in a healthy joint, or like cells in a diseased arthritic joint. This means that hopefully we can replicate these findings in the future in patients with joint injuries to help cartilage cells behave more like a those in a healthy joint in order to achieve proper cartilage healing after injury.

Next steps of this research project.

We now aim to develop 3D models of these cells in the laboratory to more closely replicate how they exist in the body and to understand how they behave when exposed to different inflammatory cell populations in this environment.

We also aim to understand in more detail what the ‘best’ kind of biological therapy would be for cartilage injury and test this out in the laboratory environment.

Publications and presentations related to this fellowship.

Two International Presentations:

1. Can we use MSC-polarised macrophages to influence chondrocyte cell behaviour and improve cartilage repair? Poster Presentation, Osteoarthritis Research Society International conference, Vienna, 2024.
2. Can we use MSC-polarised macrophages to influence chondrocyte cell behaviour and improve cartilage repair? Oral Presentation, European Orthopaedic Research Society Conference, Porto, 2023.

Impact of this Orthopaedic Research UK fellowship on your research and career

This fellowship has allowed me to conduct a full-time year-long MPhil research Master’s degree at the University of Cambridge, Department of Surgery. It has allowed me to spend dedicated time in the laboratory understanding how cells involved in cartilage repair interact and influence each other. This would not have been possible without the support of Orthopaedic Research UK and the British Orthopaedic Association. This has been a critical step to my personal development as a researcher and orthopaedic surgeon and will allow me to apply for further funding to complete a doctoral degree (PhD). I believe I will be a better surgeon for having had this supported research time, allowing me to understand how to investigate and address gaps in treatment at the fundamental level in the laboratory, and considering the all-important steps to translate this into the clinical arena.

CASE STUDY 570

BOA – ORUK: Cambridge University Hospitals

Mesenchymal stromal cells in cartilage regeneration: defining the immunomodulatory characteristics on macrophage populations

 Researcher: Alexandra Macmillan.

Supervisor: Professor Andrew McCaskie

University or Trust: University of Cambridge

Award stream: BOA/ORUK Joint Research Fellowship 2023.

Award duration: 1 year.

Amount rewarded: £60,000.

Other funders: British Orthopaedic Association