An international research team led by University of Manchester scientists has generated human kidney tissue within a living organism which is able to produce urine. The results appear in the journal Stem Cell Reports.
“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,” said co-author Professor Adrian Woolf, from the University of Manchester.
“So we are tremendously excited by this discovery — we feel it is a big research milestone which may one day help patients.”
Kidney glomeruli (constituent parts of the organ) were generated from human pluripotent stem cells grown in laboratory culture dishes. 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 — the microscopic structural and functional units of the kidney — had formed.
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. Tiny human blood vessels had developed inside the mice which nourished the new kidney structures.
However, the mini-kidneys lack a large artery, and without that the organ’s function will only be a fraction of normal.
So, the researchers are working with surgeons to put in an artery that will bring more blood the new kidney.
To test the functionality of the new structures, they used dextran — a fluorescent protein which stains the urine-like substance produced when nephrons filter the blood, called glomerular filtrate.
Dextran was tracked and detected in the new structures’ tubules, demonstrating that filtrate was indeed being produced and excreted as urine.
“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 senior author Professor Sue Kimber, also from the University of Manchester.
“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.”
Ioannis Bantounas et al. Generation of Functioning Nephrons by Implanting Human Pluripotent Stem Cell-Derived Kidney Progenitors. Stem Cell Reports, published online February 8, 2018; doi: 10.1016/j.stemcr.2018.01.008