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Stem Cell-Mediated, Functional Human Kidney Grown Inside Live

The mammalian kidney generates and eliminates waste products and is essential for life. Annually, 2.6 million people worldwide receive dialysis or kidney transplantation for end-stage kidney disease (ESKD), while around 2.2 million people with ESKD die prematurely, unable to access treatment.

In hopes to remedy this dire situation, scientists at the University of Manchester have, for the first time, developed fully functional human kidney tissue which possesses the capability of producing urine within mice using stem cells.

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 chronic kidney disease, a long-term condition where the kidneys don’t work as well as they should, affecting the lives of sufferers in various ways.

Researchers at the university, headed by Prof. Sue Kimber started off with human embryonic stem cells grown in a culture broth specifically designed for kidney development. They then turned these cells into microscopic kidney pieces. They further encouraged the cells to into forming the kidney glomeruli.

These are small units that form the basic filtration components of the kidney. They were created in petri dishes by

growing the stem cells in a nutrient broth that contained all the molecules needed to push them down the path to forming the glomeruli.

These cells were then combined with a gel in order to form a scaffolding to hold the glomeruli together, and act in effect like the connective tissue in real kidneys. The tissue clumps were then injected under the skin of mice with their immune systems repressed so as to accommodate these tiny clumps of foreign tissue, and allowed to develop.

Cross section of a functioning nephron grown by the team (University of Manchester)

A final observation, three months later showed that nephrons had appeared, including many of the associated structures, from proximal and distal tubules to Bowman’s capsule and the Loop of Henle. The team showed that fluorescent dye, injected into the mice, was being filtered from the blood and into the kidney tubules.

The tubule’s job is to selectively reabsorb key molecules, mainly salts but also things like glucose, to stop them being wasted, and we saw that as well,” added Professor Kimber. “It’s not equivalent to a kidney – we only had a few hundred nephrons and a human kidney has millions – but it has all the elements from blood flow in, up to the exit at the ureter – which takes the urine away.

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. “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.”

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