Feb 09, 2018 |
Scientists create functioning kidney tissue
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(Nanowerk News) Scientists have successfully produced human kidney tissue within a living organism which is able to produce urine, a first for medical science.
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The study led by Professors Sue Kimber and Adrian Woolf from The University of Manchester, signifies a significant milestone in the development of treatment for kidney disease.
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The Medical Research Council and Kidney Research UK funded project is published in the journal Stem Cell Reports ("Generation of Functioning Nephrons by Implanting Human Pluripotent Stem Cell-Derived Kidney Progenitors").
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Kidney glomeruli - constituent microscopic parts of the organ- were generated from human embryonic stem cells grown in plastic laboratory culture dishes containing a nutrient broth known as culture medium, containing molecules to promote kidney development.
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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.
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After three months, an examination of the tissue revealed that nephrons: the microscopic structural and functional units of the kidney - had formed.
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The new structures contained most of the constituent parts present in human nephrons - including proximal tubules, distal tubules, Bowman's capsule and Loop of Henle.
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Tiny human blood vessels - known as capillaries- had developed inside the mice which nourished the new kidney structures.
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However, the mini-kidneys lack a large artery, and without that the organ's function will only be a fraction of normal.
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So, the researchers are working with surgeons to put in an artery that will bring more blood the new kidney.
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To test the functionality of the new structures, the team used Dextran - a fluorescent protein which stains the urine-like substance produced when nephrons filter the blood, called glomerular filtrate.
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The Dextran was tracked and detected in the new structures' tubules, demonstrating that filtrate was indeed being produced and excreted as urine.
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"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," said Professor Kimber.
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"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.
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"Though this structure was formed from several hundred glomeruli, and humans have about a million in their kidneys - this is clearly a major advance.
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"It constitutes a proof of principle- but much work is yet to be done."
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The University of Manchester's School of Biological Sciences and Manchester Regenerative Medicine Network (MaRM) as well as Kidneys for life have also supported the work.
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Professor Woolf, who is also Consultant in Paediatric Nephrology at Royal Manchester Children's Hospital, Manchester University NHS Foundation Trust, 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.
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So we are tremendously excited by this discovery - we feel it is a big research milestone which may one day help patients.
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"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.
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