For the first time ever, scientists have been able to induce human stem cells into developing into functioning kidney tissue.
The researchers started by taking human stem cells in the lab, and encouraging them to form into what are known as 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. These little clumps of tissue were then injected under the skin of mice that had had their immune systems repressed, and allowed to develop.
Three months later, and examination of these lumps showed some really incredible development, the authors report in Stem Cell Reports. Tiny human capillaries had grown into the tissue, providing nutrients to the microstructures that had formed. Microscopic examination 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.
Testing the functionality of this kidney tissue, the team were able to determine that while it lacked any arteries supplying it with blood to filter – having to rely instead on the less efficient capillaries – it was still doing its job. They detected that the nephrons were indeed producing a substance known as glomerular filtrate, which is the product first produced before it is concentrated down into urine and excreted.
“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,” explained Professor Sue Kimber from the University of Manchester, UK. “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.”
Without a supply of blood through an artery, the function of such tissue is always going to be limited. The researchers also need to now work out how to develop an exit route for the urine, lest it simply build up and up in the tissue, which is of no use to anyone.
As always, this is but a single step in a journey of many. While the researchers have managed to show that kidney-like structures formed from several hundred glomeruli developed from human stem cells can seemingly function, a full-sized human kidney contains about a million glomeruli. “It constitutes a proof of principle – but much work is yet to be done,” said Professor Kimber.