Radbod Darabi, assistant professor of medicine at the University of Minnesota in Minneapolis, was awarded an MDA research grant totaling $380,049 over a period of three years to develop methods to use cells derived from skin to regenerate muscle tissue in a model of Duchenne muscular dystrophy (DMD).
A promising strategy to repair damaged muscles in DMD is to transplant healthy cells into the muscle. One source for such cells is from stem cells, which can be grown in a laboratory dish and treated to become muscle cells. In addition, stem cells can generate muscle satellite stem cells, which are normally found in healthy muscle and are necessary for long-term muscle regeneration.
Recent developments in stem cell biology have allowed researchers to generate induced pluripotent stem cells (iPS cells) from skin cells. Darabi has demonstrated that human skin-derived iPS cells are able to differentiate into muscle and can be successfully transplanted into mice that model DMD. The mice are able to accept the new cells, and the cells produce the dystrophin protein. Lack of dystrophin causes the symptoms of DMD.
“This strategy opens a new window of opportunity to use patient-specific pluripotent stem cells for disease modeling as well as cell therapy for muscular dystrophies,” Darabi says.
His work will include optimizing cell delivery and survival strategies, as well as exploring whether treating cells before transplantation with a regulatory gene can improve the long-term success of the graft. The gene, called PAX7, is a master regulator of muscle satellite stem cells.
Darabi says his research is aimed at making cell transplantation a viable treatment in DMD. “Answering these questions will be crucial for the evaluation of the therapeutic potential of human iPS cells, and consequently moving this strategy one step closer to future clinical trials in muscular dystrophy patients.”
Funding for this MDA grant began Feb. 1, 2013.