Fan Yang, PhD, a CVI member and assistant professor in orthopedic surgery and bioengineering, has been honored as one of MIT’s Technology Review magazine’s 35 under 35. The magazine’s annual honor recognizes notable inventors, thinkers and innovators who are under 35 years of age.

The achievement that garnered the magazine’s attention was developing a new system for overcoming a significant roadblock to stem cell transplantation. “Cells tend to grow well in the lab, where we can simply add growth factors,” Yang says. “But when we move to small animals or humans these cells tend to fail.” The problem, Yang explains, is that growth factors diffuse and decay very quickly in animal or human tissue, so stem cells are not able to hook up to blood vessels that bring them food and take away their waste. 

“One of the major differences in how we are approaching this is that we are using the cells themselves as the delivery vehicle for growth factors,” Yang says. By putting DNA encoding growth factors in the cells, the cells make a constant supply of the molecules the cells need to link up to the vascular system.

Yang’s second innovation is how she gets the DNA into the cells. Traditionally, researchers use viruses to bring DNA into a cell and integrate it into the cell’s genome. While this is fine for research, it is dangerous for engineering new human tissue because viruses inject DNA at random sites, which may interfere with cells natural functions or promote the unregulated cell growth and tumor formation.

Instead of a virus vector for the DNA, Yang and her colleagues use a biodegradable polymer that carries a loop of DNA into the cell. “The benefit of the materials approach is that once the DNA enters the cell, the polymer degrades and releases it,” Yang says. Furthermore, because the gene for the growth factor along with all the necessary DNA promoter is packaged in a self-contained loop, it doesn’t get integrated into the cell’s DNA and risk dangerous changes in cell function.

The system seems to work, Yang says, despite the fact that no one really understands exactly how it works. In order to find the right polymers to carry the DNA into the cell, Yang uses high-throughput screening of many, many candidate molecules, most of which do not work. “We use combinatorial chemistry to find the right material to get the DNA into the cells without killing them,” she says.

Yang and her colleagues have demonstrated the efficacy of the system in a limb ischemia model, wound healing, and bone growth in the skull. “We are also looking at it as part of a treatment for diabetic ulcers, for which there is a huge demand,” she says.

“Solving the problem of blood vessel growth would have huge impacts because it is the prerequisite for growing anything in the body,” Yang says. 

2011