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- Epilepsy
- Bone disease
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- Creating knockout tissues
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Bone disease
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2010 – 2012 Research Technician Fellowship Development of new methodologies for the 3D in vitro study of bone diseaseDr B. Evans, Dr D. Mason, Dr A. Sloan, Dr J. Ralphs & Professor J. Gregory |
The only currently available methods to study different types of bone cells together whilst in 3D are in vivo animal or whole human systems. Animal studies take place in mice, rats, rabbits, dogs and sheep. Up to 30 large animals (or up to 100 mice and rats) are used in each type of experiment.
While ethical constraints limit what can be done in humans, bone-related research in animals often falls into moderate or substantial severity categories. Animal experiments include:
- Rats suspended by their tails for 14 days to determine effects of taking the weight off their hind legs on bone quality.
- Very large holes or fractures made in rabbit legs or skulls so that newly developed substances aimed at improving bone healing may be tested.
- Larger animals like dogs & sheep are used for multi fragmentary fracture models where the the bone is fractured in several places along the length of the bone to understand bone healing in different circumstances.
Bone pathologies (e.g. osteoporosis, osteonecrosis, arthritis-related bone loss, non-healing fractures) are major public health problems and lead to significant morbidity, mortality and healthcare expenditure. Despite several recent new treatments, none of which being ideal, the challenge remains to develop further treatments and preventative regimes.
The Research Group hopes to use innovative systems that maintain human bone cells in 3D as they would be of great interest in this field, and human models allowing investigation of human bone cell interactions would represent a significant advance in understanding bone biology.
The Research Group proposes to develop two different 3D model systems to maintain human bone cells as co-cultures in vitro. The first one will enable the most abundant bone cell type, the osteocytes, to be maintained in 3D collagen gels, whilst being able to communicate with another cell type (e.g. the osteoblasts) layered on the gel surface. The second one is an organotypic method of maintaining human long bone slices in vitro.
Once established the methods will be further validated by applying them to two ongoing projects:
i) the aetiology of osteonecrosis in childhood leukaemia
ii) signalling between bone cell types following mechanical loading.
These new entirely human-derived models will both reduce animal suffering, and more accurately represent human bone diseases, enabling researchers world-wide to undertake meaningful bone research using human material.

