Stem cells isolated from the urine of healthy donors stimulated regeneration of acutely injured kidney tissue in a preclinical study conducted by researchers at Vanderbilt University Medical Center.
If confirmed by further research, these findings, reported March 29 in the journal Molecular Therapy, may lead to an effective response to acute kidney injury (AKI), which affects 50% of adults and 25% of children in hospital intensive care units.
AKI is a sudden decrease in kidney function that can lead to kidney failure, the need for kidney dialysis and death.
Diabetes, high blood pressure and advanced age are primary risk factors. AKI also can occur when injured muscles release protein into the bloodstream (rhabdomyolysis), and it is a common complication in patients hospitalized for sepsis and heart conditions and following surgery.
Urine-derived stem cells (USCs) are stem cells likely originating from the kidney that, when isolated and cultured from urine samples, can differentiate into a wide range of cell types. In animal models, USCs have accelerated wound healing, formed new joint cartilage, and reduced blood glucose levels by improving pancreatic islet function.
In the current study, Lauren Woodard, PhD, assistant professor of Medicine and Biomedical Engineering, and her colleagues isolated USCs from the urine of healthy, young adult donors.
They engineered the cells to express the gene for luciferase, the enzyme that causes fireflies to glow, and, in collaboration with Neal Paragas, PhD, of the University of Washington, used advanced imaging techniques to track the cells’ movement in live animals.
When injected into the abdomen in a mouse model of AKI, the USCs “homed” to the sites of injury in the tubules and glomeruli (the kidney’s blood filtering units) within three hours.
“They went straight to the injured kidney,” Woodard said.
During the next 24 hours, expression of a protein called KIM-1, a marker for kidney injury, fell, suggesting that the stem cells were becoming a part of, and regenerating, the damaged kidney.
Similarly, USCs were incorporated into, and reduced KIM-1 expression, in human kidney organoids, cultured tissue used to study kidney function in the laboratory.
“Our study suggests that USCs should be further developed as a potential targeted cell therapy for amelioration of acute kidney injury,” the researchers concluded.
Julie Bejoy, PhD, a postdoctoral fellow in the Woodard lab who is supported by an American Diabetes Association fellowship, is the paper’s first author.
Other VUMC co-authors are Richard Welch, Eddie Qian, and Felisha Williams, MS, from the Woodard lab, Katherine Gibson-Corley, DVM, PhD, professor of Pathology, Microbiology and Immunology, and Matthew Wilson, PhD, MD, professor of Medicine.
The study was conducted in part in the Nashville VA Medical Center, part of the VA Tennessee Valley Healthcare System, and was supported in part by the U.S. Department of Veterans Affairs.
Other support from the National Institutes of Health was provided through the Vanderbilt Center for Kidney Disease, the Vanderbilt Diabetes Research and Training Center, the Vanderbilt Institute for Clinical and Translational Research, and the Vanderbilt Cell Imaging Shared Resource.
