If you accused researcher Sheng Ding, Ph.D., of going half-way in his work, you'd be paying him a huge compliment. Ding and his team at San Francisco's Gladstone Institutes have discovered a shortcut that could someday make the promise of regenerating human organs reality.
"That would be sort of an ultimate holy grail of regeneration," said Ding.
First, it helps to understand an earlier breakthrough by another Gladstone researcher, Nobel Prize-winner Shinya Yamanaka. Yamanaka pioneered a technique to turn skin cells into what are known as induced pluripotent stem cells. Although they can turn into any cell in the body, scientists have struggled to overcome potential side effects.
"It is great that it can turn into everything, but it's also a cancer risk because it can turn into everything," said Deepak Srivastava, M.D., Ph.D., director of the Gladstone Institute of Cardiovascular Disease.
Instead of introducing genes that would take skin cells back to the stem cell stage, Ding's team developed a method to take them half-way to a state known as endoderm cells. Then, using a cocktail of small molecules, they coaxed them into becoming the specific adult cells they wanted.
The technique was so successful that it worked not just once but on multiple occasions. By collaborating with researchers at UCSF, the Gladstone team was able to create cells that mimic three separate human organs.
First the team created insulin-producing cells, which they transplanted into mice with symptoms of diabetes. After several weeks, their glucose levels fell back to normal.
"We believe we cured those mice in Type I diabetes," said Ding.
Next the Gladstone team turned skin cells into beating heart cells, known as cardiomyocytes. Srivastava believes the method may be simpler than gene therapy techniques currently being developed for heart disease.
"Ideally, you'd rather not introduce new genes into people, but use a drug, or drug-like molecules. Dr. Ding's work is pointing us to cocktails of drugs that we might be able to do the same thing with," said Srivastava.
Finally, the team was able to create human liver cells and get them to function in mice and that's touched off hope for a method to someday eliminate the need for human organ transplants.
"We think that the approach that [Ding] is taking of going and taking a cell only partway back and then redirecting it, is applicable not to just the three cell types that he's done, but probably most cell types in the human body," said Srivastava.
As for the quiet and understated Ding, he's envisioning a day when the small molecule cocktail could be delivered orally, coaxing failing organs back to health with a simple pill.
According to researchers, one of the most promising findings is that the transplanted liver cells showed no signs of slowing down after more than nine months, suggesting that the molecules used to create them could have the potential to regenerate liver tissue.
Written and produced by Tim Didion