Mayo Clinic Scientists Find New Way to Up Safety Factor of Stem Cell Therapy by Causing Contaminated Cells to Purge Themselves
Published: Sep 27, 2012
Now, researchers at the Mayo Clinic, Rochester, Minn., think they might have found an answer. Reporting in the October issue of STEM CELLS Translational Medicine, they detail a low-cost, highly-effective way to detect and then purge at-risk cells during an early stage in the differentiation process.
“Strategies to improve the safety of stem cell therapy have generally focused on separating or depleting damaged cells after the cells have differentiated. However, while this method was able to diminish the number of tumors formed as well as significantly reduce their size, the technical burdens and cost of specialized reagents and equipment needed to do so remain a challenge for widespread clinical applications,” says lead investigator Timothy J. Nelson, M.D., Ph.D. He directs the cell biology group within the clinic’s Regenerative Strategies team.
Instead, the Mayo team turned to a relatively simple protocol that involves pre-treating cultured stem cells with a genotoxin — an agent that sniffs out gene mutations or chromosomes changes in contaminated cells and kills them — after first priming the cells through the up-regulation of Puma protein, which can be activated to send a series of signals leading to cell suicide. They tested their theory using stem cells taken from a mouse model.
The results showed that not only did the contaminated cells die off, “At the same time, it didn’t affect the remaining healthy cells’ capability to differentiate nor did it have any negative consequence on their genomic stability,” Nelson says. “And it worked on stem cells derived from both natural and bioengineered sources.
“This novel strategy, based on innate mechanisms of pluripotent stem cells, is primed for high-throughput and cost-effective clinical translation.”
“The potential for tumor formation has been a significant drawback to therapeutic use of certain cell populations,” said Anthony Atala, M.D., Editor of STEM CELLS Translational Medicine and director of the Wake Forest Institute for Regenerative Medicine. “The strategy outlined in this manuscript shows promise for avoiding the risk of uncontrolled cell growth upon transplantation.”