Stem Cells Grow Mini-Kidney

Scientists have coaxed human stem cells to grow different structures found inside working kidneys. The advance is being called an important step toward the goal of growing functional organs from patients’ stem cells once their own kidneys fail.

A research team in Australia and The Netherlands report today in the journal Nature that they were able to grow tiny kidney-like organoids with a complex of different kidney cell types. Over the course of 20 days, the cultured cells differentiated and grew into an organoid containing 500 kidney cells known as nephrons. That substantial number is equal to the state of a more than 14-day-old mouse embryo’s kidney, write Minoru Takasato and colleagues. Comparing the engineered tissue to normal human development, they found its gene expression most closely resembled that of a first-trimester fetal kidney.

“There is a long way to go until clinically useful transplantable kidneys can be engineered, but Takasato and colleagues’ protocol is a valuable step in the right direction,” writes the University of Edinburgh’s Jamie Davies, who did not participate in the research.



Davies says the work is important because finding a way to make cells that will turn into kidney cells has proven to be a major hurdle for growing kidneys in the lab. Takasato’s group brings the daunting task of starting with just a few progenitor cells and arriving at a functional kidney into stark relief: “The human kidney contains up to 2 million epithelial nephrons responsible for blood filtration. Regenerating the kidney requires the induction of the more than 20 distinct cell types required for excretion and the regulation of pH, and electrolyte and fluid balance,” they write.

To start the long process of overcoming this obstacle, the group identified the developmental mechanisms that trigger progenitors to turn into specialized kidney cells. With this knowledge they were able to push progenitors to develop into either the kidney cells that form collecting ducts, connective tissue and blood vessels in the organ or functional nephrons that do the filtering work of the kidney.

“Is it is possible to direct human pluripotent stem cells to form a complex multicellular kidney organoid that comprises fully segmented nephrons surrounded by endothelia and renal interstitium and is transcriptionally similar to a human fetal kidney,” the team writes. “As such, these will improve our understanding of human kidney development.”



These mini-kidneys won’t be useful for transplants anytime soon–they lack the organization and plumbing that a fully developed kidney requires to concentrate and eliminate urine. Still, the current state of their development could see them used as model tissue for drug development and toxicity screening. Tests that exposed the organoids to renal toxins showed that they were damaged in the same way that human kidneys are.

“These kidney organoids may fulfil a different medical need — the ability to test drug safety on human kidney tissue, rather than in poorly predictive animals,” writes Davies. “The cell types that are most vulnerable to damage by drugs are present in the organoids, and the authors provide preliminary evidence to demonstrate that the system is indeed damaged by a known renal toxin.”



With news coming earlier this week about mini-brains now being made cheaply and easily for better laboratory testing and modeling of actual human brains, observers have gotten a glimpse inside the rapidly advancing world of tissue engineering.

Gifs created from Youtube videos courtesy of Minoru Takasato.