Scientists know people react differently to medication because of their genetic make-up. However, while researchers understand certain genetic variations correspond with certain responses to drugs, they aren't sure why.
A study published in the journal Stem Cells Translational Medicine by two members of the UF Genetics Institute - Naohiro Terada, M.D., Ph.D., a professor in the UF department of pathology, immunology and laboratory medicine, and Julie Johnson, Pharm.D., dean of the UF College of Pharmacy, details their efforts to unravel the "why."
To better understand how genetic variations translate to differing drug responses, researchers need to be able to study human genetics in a dish. Mouse models simply are not sufficient, and obtaining cells that contain genetic information from certain organs in humans can be difficult.
To resolve this, the researchers in this study extracted blood cells from a number of patients with high blood pressure, converted those blood cells into pluripotent stem cells - cells capable of developing into any kind of human tissue. These pluripotent stems cells are then converted into vascular smooth muscle cells.
Creating vascular smooth muscle cells - or the particular organ cells researchers need - from blood cells allows the researchers to study human cells that they would not be able to obtain from otherwise healthy people with high blood pressure. This also enables researchers to analyze cells that contain the patients' genetic information. Using these samples, the research team was able to study how genetic differences cause some people to respond better or worse than others to medication.
"This is an institutional effort to try to develop stem cell-based research for advancing precision medicine," Terada said.
Johnson's lab identified genetic markers related to differential responses to anti-hypertensive drugs, while Terada's lab developed the pluripotent stem cells. In collaboration, the researchers also created a stem cell repository from participants in clinical studies of the antihypertensive drugs, for which genomic data and individual responses to medications are available. They also developed a highly efficient method for converting stem cells into functional vascular smooth muscle cells.
"This is a very inaugural paper for us because we developed both resources and a reliable method to differentiate stem cells," Terada said.
Using the methods established here, the researchers are now actively working on understanding why certain genetic markers correspond to certain reactions to hypertensive medication. UF co-authors of the paper include Niki Biel, Ph.D., Katherine Santostefano, Ph.D., and Bayli DiVita in the department of pathology, College of Medicine; Nihal El Rouby, Rhonda Cooper-DeHoff, Pham. D., in the department of pharmacotherapy, College of Pharmacy; and Santiago Carrasquilla and Chelsey Simmons Ph.D. in the department of mechanical and aerospace engineering, College of Engineering.