New study reveals potential instability in stem cells

New study reveals potential instability in stem cells

Madison, Wis. – When you don’t use or refrigerate your dairy products, they spoil beyond use – and now it looks like stem cells may have the same problem. Except instead of food poisoning, this problem could lead to cancer.
A new study in the magazine Nature Genetics claims that human embryonic stem cells, one of the few cell types that self-renew, show deviations in their genetic structure when left to replicate. Published in an advance online issue Sunday, the article highlights risk to the use of embryonic stem cells in human treatment, and calls the existing supply lines into question.
The findings of mutation in stem cells are nothing new to researchers, according to Stephen Duncan, an associate professor of cell biology, neurobiology and anatomy at the Medical College of Wisconsin in Wauwatosa. What makes the survey significant, however, is that it is the first in-depth and technically sensitive study to confirm HESC’s accumulate mutation.
“It’s better knowing about them then not knowing about them, so this is a good thing,” said Duncan, who was not involved in the research.

Don’t leave cells to own devices

The study, conducted by an international team of 24 researchers from the United States, Singapore, Canada and Sweden, studied nine pairs of early and late-passage human embryonic stem cells from federally approved lines. Three of the cell lines were controlled by the University of Wisconsin-Madison and distributed to the researchers by the WiCell Research Institute.
Stem cells are typically kept in storage by researchers, and when brought into the open they begin to replicate and have to be transported into different lab cultures. Stem cells that are activated in the real world are known as low or early passage lines, while the later cultures and cells that reproduce continuously are high passage lines.
The team studied the cells as they self-replicated, capturing images with high-resolution equipment to locate any mutations in the DNA structure. Cells were allowed to replicate between 22 and 175 times, a process which typically takes between four and five days.
At the end of the monitored replication, the researchers found that the cells had several genetic flaws, with chromosomes misplaced, switched around or even deleted from the original cells. Eight out of the nine cell lines showed aberrations in the DNA sequence and replaced hydrogen atoms, making them more consistent with cancer cells than with stem cells.
“The observation … implies that periodic monitoring of these lines will be required before they are used in in vivo applications and that some late-passage HESC lines may be unusable for therapeutic purposes,” the report said.
The findings have a negative side for stem cell research, Duncan said, since the basis of most therapeutic uses for the cells depends on them providing a neutral background to form new cells. Defects could render experimental treatments for conditions such as cardiac failure and pancreatic cancer useless, since as they adapted to the body they would also bring in harmful genetics.
“They’ve used the most popular lines, and these are showing mutations over time,” Duncan said. “Potentially, you could end up causing cancer in the person you transplant to.”

Not the end of the treatment

However, damaged cells in a lab setting do not translate to automatic cancer among patients. Gabriela Cezar, an assistant professor at the University of Wisconsin-Madison Department of Animal Sciences and part of UW’s Stem Cell Research Program, said that it is neurons, islets and other cells derived from the stem cells are the main candidates for treatment, and “raw” HESC are not used for direct treatment.
“It is critical to evaluate how the aforementioned changes impact the ability of HESC to generate these cell types, as well as the implication of these changes for the safety of the cell types generated,” Cezar said.
The cells may be able to play a more valued role in this study, as they could be used as a new tool for curing cancer. Since their growth and mutation is monitored so closely – down to the “sentence of the genome” according to Duncan – scientists could study the exact mechanisms that create cancer in a normal, healthy cell.
Experts said the real value of the cells, however, is that they display the need for a re-examination of the stem cell supply chain. Most low passage lines are free from the mutation that was studied by the research team, meaning that cells have to be as new as possible for maximum success – a problem with the existing narrow cell lines.
“The longer you passage these cells [and] keep them in culture, the more frequent these mutations will be,” Duncan said. “If you wait until longer, they’re no longer useful.”
Since there are few cell lines that rely on the early passage lines – the purest sources of all stem cells – Cezar said it is important to notice the report’s warning that we could naturally be losing federally sanctioned sources of cells. If the vulnerable genes exposed by the study are not analyzed further, many therapeutic methods could be removed.
“It is vital to deepen our knowledge of HESC prior to any clinical applications,” Cezar said.

Les Chappell is a writer for WTN based in Madison. He can be reached at