Human stem cells have been turned into clumps of kidney tissue in a crucial first step towards building new organs for patients in the lab.
Scientists in Australia made the breakthrough after turning stem cells derived from human skin into two of the main structures found in kidneys, namely collecting ducts and blood-filtering units called nephrons.
Their “organoids” are comparable to an unborn baby’s kidneys in the first trimester, and are not yet good enough to transplant into sick patients. But in the near term they will be valuable for screening drugs for toxic effects, and recreating genetic kidney diseases in a dish.
The balls of kidney tissue, which measure less than a centimetre across, also hold promise as sources of fresh kidney cells for medical treatments.
Writing in the journal Nature, Minoru Takasato and colleagues at the Royal Children’s hospital in Melbourne describe how they got cells to clump together into primitive kidneys over nearly three weeks in culture. “They spontaneously formed complex kidney organoids,” the scientists write.
After growing the organoids in the lab, the researchers found they contained not only collecting ducts and nephrons to filter blood, but cells that form the connective tissue and blood vessels normally seen around nephrons in foetuses.
The human kidney contains up to 2m nephrons which clean the blood by removing urea, salts and excess water. The fluid forms urine which is gathered by collecting ducts and passed through ureters to the bladder.
Until now, scientists have struggled to get stem cells to form different cell types found in the kidney. But the Australian group solved the problem in a series of experiments that perfected the chemical signals stem cells need to receive to form early stage collecting ducts and nephrons.
To test whether the organoids reacted to toxic drugs in the same way as healthy human kidneys, the scientists exposed them to the cancer drug, cisplatin, and found that they suffered similar damage.
In an accompanying article in the same journal, Jamie Davies at the Centre for Integrative Physiology at Edinburgh University, explains that with kidney disease on the rise, and a shortage a transplantable organs, one solution is to build human kidneys from stem cells.
In the year to April 2013, the NHS performed about 3,000 kidney transplants in the UK, though more than 6,000 patients were left on the waiting list.
But Davies stresses that the organoids are not fully-functioning kidneys. “There is a long way to go until clinically useful transplantable kidneys can be engineered,” he writes, adding that Takasato’s work is “a valuable step in the right direction”.
The organoids are still likely to be valued for other uses in medicine though. As Davies adds: “These kidney organoids might fulfil a different medical need – the ability to test drug safety on human kidney tissue, rather than in poorly predictive animals.”
“The result could be a major step towards animal replacement and improved safety screening for drugs, as well as towards transplantable kidneys,” he adds.
In August, scientists at Ohio State University claimed to have grown an immature brain in the lab for the first time. The ball of brain cells, no larger than a pencil eraser, could be used to test drugs for neurodegenerative diseases, such as Parkinson’s and Alzheimer’s.
The work followed reports from others stem cell scientists who created pea-sized miniature stomachs for studying gastric diseases, and rudimentary eyes, aimed at helping researchers to study and ultimately treat blindness.