S. Kimber et al, Manchester University
Scientists create functioning kidney-like tissue from stem cells
9 Feb 2018
Scientists have successfully produced human kidney-like tissue within a living organism, which is able to produce urine. The study authors, led by Professors Sue Kimber and Adrian Woolf from the University of Manchester, said it greatly advances our progress toward using stem cells to repair damaged kidneys.
The scientists generated glomeruli – one of the functional components of a kidney – from human embryonic stem cells grown in laboratory culture dishes with a nutrient broth, containing molecules to promote kidney development.
They were combined with a gel-like substance, which acted as natural connective tissue, and then injected as a tiny clump under the skin of mice.
After three months, an examination of the tissue revealed that nephrons – which filter waste from blood and produce urine – had formed. The new structures contained most of the constituent parts present in human nephrons.
Tiny human blood vessels, known as capillaries, had also developed inside the mice, which nourished the new kidney structures.
To test the functionality of the new structures, the team used dextran – a fluorescent protein which stains the urine-like substance (glomerular filtrate) produced when nephrons filter blood. The dextran was tracked and detected in the new structures’ tubules, demonstrating that filtrate was indeed being produced and excreted as urine.
However, the scientists noted that the mini-kidneys lacked a large artery, without which the organ’s function would be limited. The researchers said one of their next steps is to work with surgeons to put in an artery that will bring more blood to the new kidney.
Professor Kimber said: “We have proved beyond any doubt these structures function as kidney cells by filtering blood and producing urine – though we can’t yet say what percentage of function exists.
“What is particularly exciting is that the structures are made of human cells which developed an excellent capillary blood supply, becoming linked to the vasculature of the mouse. Though this structure was formed from several hundred glomeruli – and humans have about a million in their kidneys – this is clearly a major advance. It constitutes a proof of principle, but much work is yet to be done.”
Professor Woolf, said: “Worldwide, two million people are being treated with dialysis or transplantation for kidney failure, and sadly another two million die each year, unable to access these treatments. So we are tremendously excited by this discovery – we feel it is a big research milestone which may one day help patients.
“However, there is much more to learn: building on our generation of kidney filtration units we must now turn to developing an exit route for the urine and a way to deliver this technology to diseased kidneys.”
- The work was also helped by a small grant from local Manchester kidney charity Kidneys for Life.