Every year, more than 130,000 people in the U.S. are diagnosed with end-stage kidney disease, with most cases caused by diabetes. Newer therapies show promise to slow kidney failure rates, but none stop progression to end-stage kidney failure.
"It is going to take a multipronged approach. By utilizing cell-based therapies, we can really begin to target proinflammatory pathways that contribute to kidney disease onset and subsequent progression," says Dr. Hickson, who is chair of the Mayo Clinic Division of Nephrology and Hypertension in Florida. "The beautiful thing about cell-based therapy is that it has anti-inflammatory and immunomodulatory repair properties that help fight disease with potentially fewer side effects compared to traditional immunosuppressants used in clinical practice."
Regenerative biotherapeutics seeks to deliver new cell and gene therapies that restore health. Mayo Clinic's Center for Regenerative Biotherapeutics is at the forefront of this movement and supports Dr. Hickson's research as part of its objective of delivering new cures to the practice.
Promising preclinical data
Dr. Hickson's research seeks to answer the scientific question, "Could stem cells provide a new option for restoring kidney health?"
"Our theory is that stem cells could provide an anti-inflammatory intervention to lessen inflammation and stop the scarring that destroys diabetic kidney structure and function. Preclinical data show that cell-based therapies, such as mesenchymal stem cells, reduce inflammation and scarring, and improve kidney tissue oxygenation. We documented this without the side effects that come from anti-inflammatory drugs," says Dr. Hickson.
Dr. Hickson's research focuses on the use of mesenchymal stem cells for treating diabetic kidney disease in preclinical models and in humans. Mesenchymal stem/stromal cells are adult stem cells with the ability to differentiate into multiple cell lines and release repair factors with healing activities in the kidney.
"My enthusiasm for regenerative therapies initially came from my mentors’ research, which demonstrated an improvement in kidney function in preclinical models after injecting mesenchymal stem cells into constricted renal blood vessels," says Dr. Hickson. "In our phase I clinical trial using a patient's own mesenchymal stem cells as a therapy for renovascular disease, we documented a reduction in pro-inflammatory factors circulating in the blood while noting improvement in kidney oxygen levels. Data showed improved kidney function at three months."
In the next step of her research, Dr. Hickson's team is applying these findings in two early-phase clinical trials that test the use of mesenchymal stem cells from healthy donors for treatment of diabetic kidney disease.
"Kidney damage cannot be reversed once is goes beyond a certain point. Our goal is to try to limit the number of people who are progressing to end stage kidney failure." LaTonya Hickson, M.D.
The challenge of diabetic kidney disease
The Centers for Disease Control and Prevention estimates that 1 in 7 adults, or 37 million people in the U.S., have chronic kidney disease that could eventually progress to kidney failure. Diabetic kidney disease is the most common cause.
"Unlike in the liver, where there is more robust intrinsic regenerative capacity, kidney damage cannot be reversed once it goes beyond a certain point," says Dr. Hickson. "Our goal is to try to limit the number of people who are progressing to end stage kidney failure so they can have a better quality of life and a longer health span."
Dr. Hickson's interest in cell-based solutions for diabetic kidney disease has roots in her training at Mayo Clinic and other schools.
Following graduation from the University of Louisville School of Medicine, Dr. Hickson completed her residency at Wake Forest University Baptist Medical Center. She did a fellowship in nephrology in the Mayo Clinic School of Graduate Medical Education within the Mayo Clinic College of Medicine and Science.
Dr. Hickson's research of therapeutic potential in preclinical models provides the framework for phase I safety studies in humans. Further clinical trials are needed to verify effectiveness of mesenchymal stems cells in treating diabetic kidney disease and chronic kidney disease. Depending on the outcome, it could take 10 years or more before cell therapy for diabetic kidney disease is available for daily clinical care.
In a Phase 1a escalating clinical trial, autologous mesenchymal stem cell infusion for renovascular disease increases blood flow and the glomerular filtration rate while reducing inflammatory biomarkers and blood pressure.