It’s been estimated that up to 45% of all deaths in the developed world can be attributed to fibrotic disorders, where connective tissue starts to replace normal tissue, resulting in permanent scarring and reduction of organ function. In the UK alone, the cost for treatment of glomerular fibrosis and other chronic kidney disease is estimated to be £2bn each year. Current models used to investigate potential treatment compounds fall far short of the needed criteria to provide accurate assessments - seven out of every eight drugs which reach the final stages of drug development fail - two thirds of these due to unforeseen renal toxicity.

Dr Gavin Welsh, Reader in Renal Cell Biology at the University of Bristol, is part of the Bristol Renal group, which has used tissue-engineering and materials science to develop a 3D cell model of kidney fibrosis far superior to those in use currently.

Accuracy

With help from the TRACK award from the Elizabeth Blackwell Institute, the Group has demonstrated that the model - developed by Dr Jack Tuffin - more accurately simulates the disease than any current industry-standard approaches.

Dr Welsh said, “The purpose of the model up until now has been to study the underlying mechanisms of kidney fibrosis and is being used for that routinely here at Bristol Renal.

“The ultimate goal, though, is to greatly expand on the model, so that it can be used to screen a library of drugs, as well as to stratify patients in the later stages of clinical trials. By improving the earliest stages of the drug discovery process, we will hopefully advance the discovery of new anti-fibrotic therapies.”

The future is 3D

Current industry-standard approaches use 2D cell models which very poorly simulate kidney fibrosis; there’s very little industrial research focusing on replacing these models, so academia must step in. There has been great progress in recent years on kidney organoids which are formed from stem cells. These organoids, whilst a far better representation of a real kidney, are not nearly scalable enough to replace current 2D models used in early drug discovery. This means that whilst they are useful at later stages, they are not the innovation that is required.

Bristol Renal group’s model grows human kidney cells in a 3D environment, which is much closer to human kidney tissue than the currently used models.  The result is a model of glomerulosclerosis - scarring of the glomeruli capillaries in the kidney - that far more accurately represents the disease.