Research Themes
1. Skin and Laminar Structures
Headed by Professor Mark Ferguson
Dermal scars are a significant cause of physical and psychological
problems. Each year, around 74 million people undergo elective
surgery that leads to scarring. Following trauma (18.5 million/year),
or burns (6.6 million/year) it is a significant clinical problem,
particularly in children (picture), as it restricts growth
and function. Chronic wounds, which fail to heal, are common
in the elderly, impose a burden on the individual, and account
for 50% of community nursing time and so are costly to treat.
The Manchester wound healing group has investigated age, sex
and disease-related changes in human wound healing, with a
view to instituting rational preventative or therapeutic measures.
Nevertheless, radical improvements in tissue engineered skin
products are required to make them an effective and economic
treatment for victims of trauma, burns, surgery, and to accelerate
the healing of acute and chronic wounds in the elderly.
2. Cartilage, Intervertebral Disc, Compressive
and Tensile Structures
Headed by Professor Tim Hardingham
Chondrocytes are responsible for the production of cartilage
ECM, but lose the ability to make ECM in cell culture. In a
new programme of work we plan to investigate the expression
of SOX genes in human chondrocytes during the loss of phenotype
in cell culture and we will establish if the expression of
transfected SOX genes causes the recovery of phenotype. The
signals from ECM that act on chondrocytes in cartilage matrix
and maintain phenotype will be identified Differences in gene
expression between chondrocytes in cartilage and passaged chondrocytes
transfected with the SOX genes will establish if other regulatory
genes are involved. The synthesis and assembly of cartilage
matrix by chondrocytes in culture will be assessed by composition
analysis, confocal microscopy, and by confocal-FRAP analysis
to monitor matrix network formation. This will identify the
key interactions in the initial assembly of ECM by chondrocytes
and will lead to new strategies for generating cartilage matrix
in culture for tissue engineering.
3. Vascular and Tubular Structures
Headed by Professor Cay Kielty
Diseases of the circulation are the largest cause of death
in the UK. We are developing small diameter vascular prostheses
for coronary and other revascularisation procedures, with appropriate
mural architecture and mechanical properties. An important
aspect of our studies is to define human vascular cells suitable
for seeding our vascular grafts. In our current experiments,
we are utilising smooth muscle cells from coronary and umbilical
arteries. Studies are also focussed on differentiating adult
mesenchymal stem cells from bone marrow and peripheral blood.
We have also established a comprehensive profile of assays
for SMC phenotype, including analysis of cytoskeleton, focal
adhesions, cell-surface receptors (especially integrins), and
production and deposition of extracellular matrix. These assays
involve analysis at mRNA and protein levels, as well as microscopy
studies of cell-matrix organisation within the vascular grafts
(immuno-histochemistry, confocal microscopy, ultrastructure).
Future cellular/ molecular studies include establishing reporter
systems to visualise expression changes during graft formation
to learn more, in real-time, about how different culture conditions
influence matrix deposition.
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