Adult Stem Cell “Successes” May Need Closer Look, UF Research Finds

March 13, 2002

GAINESVILLE, Fla. — Researchers may need to look more closely before concluding that adult stem cells can transform into other types of cells, according to University of Florida research to be published Thursday in Nature.

The UF findings suggest that much-publicized studies showing that adult stem cells from one type of tissue, such as bone marrow, can transform into other types, such as muscle or brain cells, may need to be re-examined. It may be instead that the stem cells are fusing with existing cells, the research concludes.

“I still think it would be wonderful if blood cells could turn into brain or muscle cells, but I think before concluding that, we may need to do some work,” said Dr. Naohiro Terada, an associate professor of pathology, immunology and laboratory medicine and the main author of the paper by four UF stem cell scientists in UF’s College of Medicine. “We’re saying we have to be careful before making any conclusions.”

Terada said the results derived from an attempt to make adult bone marrow cells from mice transform into embryonic cells, or the undifferentiated type of stem cells derived from discarded embryos that have shown so much potential. In that effort, Terada and his colleagues mixed bone marrow cells and embryonic stem cells, marking the bone marrow cells with a fluorescent green protein. After a few weeks, the researchers discovered green embryonic stem-like cells, which made it appear that the bone marrow cells had somehow reverted to an undifferentiated state.

“We were so excited because this method would solve a lot of current problems,” Terada said.

When researchers examined the results more closely, however, they discovered that the bone marrow cells had about 80 chromosomes – double the 40 found in typical mouse cells. More important, these cells had a “mixed genotype,” or contained genes from both the bone marrow and the embryonic stem cells. Apparently, the cells had merged. “The cells had fused somehow in the culture,” Terada said.

The researchers were disappointed, because the body would reject such cells as foreign, and so they would never be good candidates for clinical use, Terada said. But the researchers soon realized that their results could provide an alternative explanation for recent studies concluding that adult stem cells from one tissue can give rise to cells of a completely different tissue.

“People have claimed that after bone marrow transplantation, for example, they see bone marrow-derived brain or muscle cells,” Terada said. ““We now should think of alternative mechanisms such as cell fusion to explain these phenomena.”

Edward Scott, UF associate professor of molecular genetics and microbiology and director of UF’s multidisciplinary stem cell team, is a co-author of the paper. He said it may be difficult to reexamine old studies, but new studies should take the possibility of cell fusion into account. “Right now, there’s a large frenzy about how stem cells can make and do everything, every kind of tissue, and that may still be true,” he said. “But what this tells us is we have to have more controls to make sure it’s true, and our program at UF has already implemented these controls in our ongoing experiments.”

The other UF authors are Bryon Petersen and Dr. Laurence Morel, both assistant professors of pathology, immunology and laboratory medicine.