The discovery could be used to help treat kidney disease in the future, and the new structures will enable kidney diseases to be modelled, aiding research in this area.
Forming Kidney Structures
To create the human tissue in mice, the team firstly generated kidney glomeruli from human embryonic stem cells grown in plastic laboratory culture dishes containing culture medium. The glomeruli were then combined with a gel-like substance before being injected under the skin of mice as a tiny clump. Nephrons were formed 3 months later in the tissues, the structures of which held the constituent parts present in human nephrons. Capillaries had also formed in the mice, nourishing the new kidney structures.
The functionality of these structures was proven using Dextran, a fluorescent protein, to stain glomerular filtrate, which is produced when nephrons filter the blood. This showed that filtrate was being produced and excreted as urine, a potentially groundbreaking discovery.
“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 Prof Sue Kimber, 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.”
The researchers believe this could be a major milestone in the treatment of kidney disease patients. They stress, however, that this study is proof of principle only, and further work is required, including putting a large artery into the mini-kidneys to bring more blood to the new kidney. An exit route for the urine also needs to be developed, as well as a method of delivering the technology to diseased kidneys.
James Coker, Reporter