Scientists create 'mini bile ducts' to discover new drugs.
An experimental cystic fibrosis drug has been shown to prevent the disease’s damage to the liver, thanks to a world-first where scientists grew mini bile ducts in the lab.
For the first time, researchers led by scientists from the Wellcome Trust-Medical Research Council Stem Cell Instituteat the University of Cambridge and the Wellcome Trust Sanger Institute in Cambridge, used stem cells to grow fully functional three-dimensional bile ducts in the lab. Bile ducts act as the liver’s waste disposal system, and malfunctioning bile ducts are behind a third of adult and 70 per cent of children’s liver transplantations.
The researchers used their ‘miniature bile ducts’ to test new drugs for biliary disease, leading to the discovery that VX809 – an experimental compound originally designed to treat the effects of cystic fibrosis in the lungs – could be the first treatment to prevent the damage cystic fibrosis causes to the liver and bile duct.
Dr Fotios Sampaziotis, lead author and an MRC-Sparks clinical research fellow in hepatology, said:
“Treating liver complications caused by bile duct disorders constitutes a major challenge – with the only treatment option often being liver transplantation. Identifying a new experimental drug that could prevent patients with cystic fibrosis from undergoing a liver transplantation, a major and life changing operation, could have huge implications for our patients. But, this treatment will need to be tested in clinical trials before it can be recommended to patients.”
Until now there has been no way of generating large numbers of fully functional bile ducts that mimic disease in the lab, which has limited our understanding of biliary disorders and restricted the development of new drugs. Using their ‘bile duct replicas’ the researchers reproduced key features of two more bile duct diseases – polycystic liver disease and Alagille syndrome – and tested the effects of additional drugs, such as octreotide.
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Sampaziotis F, Cardoso de Brito M, Madrigal P, Bertero A, Saeb-Parsy K, Soares FAC, Schrumpf E, Melum E, Karlsen TH, Bradley JA, Gelson WTH, Davies S, Baker A, Kaser A, Alexander GJ, Hannan NRF and Vallier L. Cholangiocytes derived from human induced pluripotent stem cells for disease modeling and drug validation. Nature Biotechnology. 13 July 2015. doi:10.1038/nbt.3275