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By studying blood vessels at single cell resolution, Professor Jagdeep Nanchahal and colleagues found that in Dupuytren’s disease, a fibrotic disorder of the hand, the vasculature is key to orchestrating the development of human fibrosis.

Blood cells

The team has previously shown that development of myofibroblasts, the cells responsible for deposition of the excessive matrix and contraction, is dependent on production of tumour necrosis factor (TNF) by local immune cells. The research, published in PNAS showed that endothelial cells lining the blood vessels modulate the activity of immune regulatory fibroblasts, which secrete mediators that attract the immune cells. They also identified that a potential myofibroblast precursor cell that is contained within a compartment of cells called pericytes that wrap around the blood vessel wall.

First author on the paper, Dr Thomas Layton, who started the work the work as a Kennedy DPhil student at the Kennedy Institute said: "This study illustrates the potential of using state of the art molecular biology techniques to relatively under studied diseases."

Fibrotic diseases, such as idiopathic pulmonary fibrosis, liver cirrhosis and chronic kidney disease, all result from excessive scarring of tissues leading to progressively worsening organ function. Although these diseases have high morbidity and mortality in the Western world, research has been limited by difficulty accessing tissues at the earliest stages of disease. In contrast, in Dupuytren's disease, affected tissues from the palm of the hand are relatively easy to obtain, and can provide clues into fibrotic pathways and possible approaches to slow down or halt disease.

"Animal models fail to recapitulate all aspects of human fibrosis," said Professor Nanchahal. "The pathways we identified using tissue from patients with Dupuytren's disease also appear to pertain to other human fibrotic diseases, such as idiopathic pulmonary fibrosis."

The work was supported by an Oxford-BMS/Celgene fellowship, Royal College of Surgeons of England and British Society for Surgery of the Hand.

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