UC Davis stem researchers demonstrate safety of gene therapy using adult stem cells

Study provides key safety data for human trials

(SACRAMENTO, Calif.) — A new study by UC Davis researchers provides evidence that methods using human bone marrow-derived stem cells to deliver gene therapy to cure diseases of the blood, bone marrow and certain types of cancer do not cause the development of tumors or leukemia. The study was published online in the May 6, 2008 issue of Molecular Therapy.

"The results of our decade-long study of adult human stem cell transplantation shows that there is little risk of adverse events caused by gene transfer, and that adult human stem cells do not pose a cancer risk when implanted into different organs," said Jan Nolta, senior author of the study and director of the UC Davis Stem Cell Program.

Nolta and her colleagues tested the safety of gene transfer into bone marrow stem cells from human donors in more than 600 mice. None of the transplanted mice developed leukemia or solid tumors caused by the gene therapy treatment, during the evaluation period of up to 18 months.

"These data are critical for advancing stem cell research leading toward therapies," Nolta said. "We've shown that adult stem cells follow natural cues to reach target locations, they function normally when they get there and do not exhibit the unchecked cell growth that is the hallmark of cancer."

Gene therapy trials using human bone marrow cells began in the early 1990s and have since included roughly 1,000 patients worldwide. In 2000, a leukemia-like condition emerged in three participants in a clinical trial in France, halting the trial and calling into question the safety of the method. Researchers suspected that the gene transferred in this trial gave the transplanted cells an enhanced growth capacity that led to the cancers.

"After those studies in France, the gene therapy community felt that further biosafety testing was warranted," explained Gerhard Bauer, lead author of the study and an assistant professor of hematology and oncology. "Due to the significantly large number of study animals, our investigation further illuminates the safety of gene therapy using hematopoietic stem cells. It allows us to rest easier with the knowledge that if we insert corrective genes into human bone marrow stem cells and administer those cells to human patients, we are providing a relatively safe therapy."