Researchers at the Saban Research Institute of Children’s Hospital of Los Angeles and the University of Southern California (USC) have reported the isolation of human nephron progenitor (NP) cells. These results, which were published in the journal Stem Cell Translational Medicine, might very well elucidate how progenitor cells differentiate into become renal cells and then develop into kidneys. Such insights could, possibly provide new strategies to promote renal regeneration after chronic kidney failure or acute kidney injury.
Kidneys are composed of about a million tiny filtration units known as “nephrons.” These diminutive structures filter waste and concentrate those wastes into urine, which is leaked into the bladder. In humans, approximately 500,000 to 1,000,000 nephrons are generated before week 34 – 36 of fetal gestation. However, at this point in development, the NP cells are exhausted and kidney development (known as “nephrogenesis”) effectively ceases. If the kidney loses a large enough quantity of nephrons after this time period, such losses may lead to irreversible kidney failure, since no further cell repair or regeneration is possible.
In past studies, NPs were made from induced pluripotent stem cells, or by utilizing animal models. Scientists at USC and Children’s Hospital of Los Angeles (CHLA), chose a different tactic; they designed an efficient protocol by which they could directly isolate human NPs. To accomplish this, Dr. Laura Perin and her colleagues used RNA-labeling probes to obtain cells that expressed the SIX2 and CITED1 genes. Cells expressing both of these genes are almost certainly NPs, since SIX2 and CITED1 are master regulatory genes that promote renal development.
Dr. Perin, co-director of CHLA’s GOFARR Laboratory for Organ Regenerative Research and Cell Therapeutics in Urology, added, “In addition to defining the genetic profile of human NP, this system will facilitate studies of human kidney development, providing a novel tool for renal regeneration and bioengineering purposes.”
On a rather sanguine note, Perin noted that these experiments, which constitute proof-of-concept work, may create new applications to researchers who might be able to use her laboratory’s techniques to isolated progenitor cells for other organs, the pancreas, heart, or lung. “This technique provides a ‘how to’ of human tissue during development,” said Perin.
“It is an important tool that will allow scientists to study cell renewal and differentiation in human cells, perhaps offering clues to how to regulate such development,” added first author of this paper, Stefano Da Sacco.