Shahin Rafii's team has already shared their resources, sending mice with genetically labeled GPR125 cells, spermatogonial stem cells, and multi-potent adult stem cells derived from spermatogonial stem cells to several other laboratories.

When Shahin Rafii was a teenager in Tehran, Iran, eager to continue the family tradition of becoming a physician-scientist, the country and its universities were in turmoil that culminated in the Iranian revolution of 1977.

“It wasn't just the American hostages,” Rafii says about that difficult time. A cousin was arrested and executed. The family feared a knock on the door. It was a difficult time to get an education, yet Rafii had already become fascinated by tumor biology and the possibility of regenerative medicine. His brother, Shahrokh Rafii, a cardiologist in the United States, urged Rafii to join him and to apply to medical school. It felt like a big risk, but the dangers at home were greater. Rafii left just before the revolution began. Eventually he earned his M.D. from Albert Einstein College of Medicine.

Now an HHMI investigator at Weill Cornell College of Medicine in New York, Rafii's fascination with tumorigenesis has paid off in unexpected ways, thanks to an astute observation he made about a particularly unusual type of tumor.

In the September 20, 2007, issue of Nature, Rafii and his collaborators described how cells from the testes of adult male mice can be turned into stem cells. Moreover, the researchers demonstrated that these reprogrammed sperm-cell precursors (spermatogonia) in living mice could develop into working blood-vessel tissue as well as contractile cardiac tissue, brain cells, and a host of other cell types. If they can do the same in humans, the stem cells could potentially be used to develop treatments for men with heart and blood vessel diseases, Alzheimer's disease, Parkinson's disease, stroke, diabetes, and even cancer.

These findings have been a decade in the works, beginning when Rafii was a fellow in hematology and oncology at Weill Cornell. There, he became intrigued by teratomas—bizarre, but curable, tumors that develop primarily in the testes and ovaries. They resemble disorganized embryos with many kinds of cells—skin cells, heart cells, brain cells—and even teeth. The curious composition suggested to him that the testes might be a reprogrammable source of adult stem cells for treating patients.

Photo: Mark Mahaney

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