Perin will examine the underlying biological mechanisms by which stem cells influence the formation of fibrous tissue in Alport Syndrome, which damages tiny blood vessels in the kidneys that process waste. The inherited disorder, which has its origins in a genetic mutation of a protein in connective tissue, most often affects males and can progress to end-stage renal disease at an early age.
Working in the lab, she recently found evidence suggesting that a single injection of AFSCs can reduce kidney fibrosis, accompanied with an overall improvement of renal function and lifespan. She also found that the injected stem cells create this beneficial effect by regulating the genes involved in the progression of fibrosis.
"Amniotic fluid stem cells may represent a new cell source for tissue and organ regeneration with important advantages," said Perin.
"Dr. Perin's work with amniotic fluid stem cells will be pivotal in better understanding the natural progression of this disease which may enable viable therapies for the future,” said Roger De Filippo, M.D., associate professor of urology at Children's Hospital Los Angeles and director of the GOFARR Laboratory for Organ Regenerative Research and Cell Therapeutics at The Saban Research Institute.
For one, AFSCs appear to be more pluripotent (able to generate a broad range of cell types) than adult stem cells. Also, AFSCs sidestep any controversy involving embryonic stem cells and the use of embryos in research since they come from the amnionic fluid that surrounds a fetus during pregnancy and is discarded after delivery.
Going forward, Perin wants to find out whether multiple injections of AFSCs will have a greater impact on renal function and lifespan. She is also asking other, fundamental questions.
"Very little is known about the main mechanisms by which stem cells affect the progression of fibrosis in Alport Syndrome," said Perin. "In order to claim that stem cells can be used as an anti-fibrotic therapy, it's crucial that we understand these cellular mechanisms."
Her next-stage research will seek to identify which of the molecular signaling pathways that promote renal fibrosis are modulated by the injection of AFSCs.
The ultimate goal is to develop clinical applications for patients with this rare, life-threatening kidney disorder. Understanding how stem cells behave in an in vivo environment will set the stage for translating such laboratory-based research into viable clinical therapies, including finding a much-needed treatment that could delay or even prevent end-stage renal failure in Alport Syndrome patients and those with other forms of chronic kidney disease.