Summer Student 2017: Alexander Lanz

Alexander Lanz, Supervised by Dr Aileen Crawford at the University of Sheffield, developed a cartilage repair model to understand how joints respond to injury from trauma or diseases such as osteoarthritis. His cell culture model of osteoarthritis could replace experiments on guinea pigs, rats and rabbits.

Articular cartilage is the tissue that covers the ends of the bones in joints and is essential for smooth pain-free movement of joints. However, it’s not as good as other tissues in the body at repairing itself.

Understanding how articular cartilage repairs itself will aid in developing new treatments to stimulate natural repair, to avoid degeneration-causing joint pain and difficulty. Alexander’s work will help to replace current experiments using guinea pigs, rats and rabbits.

“This studentship has granted me the opportunity to experience the PhD/research environment and therefore allows me to make a more informed career decision. I’m personally very interested in animal free research and enjoyed learning that scientific research is possible without the need for animal products. However, it did strike me that this work is somewhat ahead of its time – replacement reagents (such as culture medium), while being very effective, were also very expensive.” – Alexander Lanz

The Science behind the Studentship

Investigation of the response of human articular cartilage to traumatic injury

Articular cartilage is the tissue that covers the ends of the bones in joints and is essential for smooth pain-free movement of joints. When the cartilage is injured through trauma or disease such as osteoarthritis, it is not as good as other tissues in the body of repairing itself. Therefore, the articular cartilage may degenerate and joint movement becomes more difficult and painful. However, we do know that there are intrinsic repair mechanisms in cartilage but we do not know how these work. Therefore, we are investigating how cartilage responds to injury to learn what the intrinsic repair pathways are so that we can use this knowledge to develop new ways of stimulating the natural repair pathways to enable a more effective repair of the cartilage. We know that cartilage can release biological agents which “call in” repair cells (stem cells) to the site of injury and stimulate them to bind to the injured surface and start the cartilage repair processes. We are currently investigating what these agents are and also investigating whether the same agents can be released from osteoarthritic cartilage.

The in vitro model of cartilage repair has potential to be useful screening model for testing new potential implant models and pharmaceuticals. In this project there is only time to investigate the use of human cartilage explants and this is an essential first step. The articular cartilage repair model should be able to be used as a tertiary screening model to reduce/replace animals currently used to study biodegradable scaffolds and polymers for their capacity to promote articular cartilage repair (reviewed in 1) and to study cartilage repair after injury (2). The in vitro articular cartilage model is flexible in that it can be used in a suitable bioreactor to apply intermittent mechanical load for those longer term experiments where this aspect is essential and would then fully reflect the in vivo situation in experiments lasting several weeks

The cartilage repair model could also be further refined by isolating the chondrocytes culturing them for a short time (one-two passages) and using them to create tissue–engineered articular cartilage constructs. This would enable more samples to be created. This aspect has not been carried out in this project due to the project time constraints.

REFERENCES: 1. Chu CR, Szczodry M, Bruno S. Animal models for cartilage regeneration and repair. Tissue Engineering part B. 2010; 16(1):105-115.; 2. Eltawil NM, De Bari C, Achan P, Pitzalis C, Dell Accio F. 2009; Osteoarthritis and Cartilage 2009; 17(6):695-704.

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