A sticky problem that is holding back the therapeutic use of stem cells bioengineered from adult tissue (induced pluripotent stem cells or iPS cells), is the risk that any residual undifferentiated ones will remain and form tumors after transplant into the patient. So while iPS stem cell therapy may be effective, as long as this problem remains, it is unsafe. Now researchers at the Mayo Clinic in the US may have found a solution: in a study published online this week they show how they purged or selectively killed the tumor-forming cells by damaging their DNA.
The study appears in a 27 September issue of the journal Stem Cells Translational Medicine.
iPS cells have properties similar to embryonic stem cells, which are “master cells” with an unlimited capacity to differentiate into any type of tissue in the body, such as brain, lung, skin, heart, and liver. Thus their potential in regenerative medicine, where damaged or diseased tissue can be repaired or replaced by growing new tissue, is huge, as senior author Timothy Nelson explains in a press release:
“Pluripotent stem cells show great promise in the field of regenerative medicine; however, the risk of uncontrolled cell growth will continue to prevent their use as a therapeutic treatment.”
Nelson is Assistant Professor of Medicine and Pharmacology and works in the General Internal Medicine department and the Transplant Center at the Mayo.
The idea of using iPS cells is for doctors to be able to take some adult tissue, for example skin cells, from the patient who needs the treatment, and then turn the cells from that tissue into iPS cells.
Then, those iPS cells are coaxed to turn into the target type of cell, for instance lung cells. As a result of the coaxing the iPS cells turn into (differentiate) the target tissue type.
But current ways of doing this leaves some iPS cells undifferentiated, so they get transplanted into the patient along with the differentiated cells, leaving the risk that they will differentiate on their own in an uncontrolled way and form tumors.
For their study, Nelson and colleagues used lab mice to show that pretreating iPS cells with a chemotherapy drug, selectively damages the DNA of the stem cells, killing them off so they cannot grow uncontrollably and form tumors. The chemotherapy kills the iPS cells by triggering cell suicide or apoptosis, which is a natural response to DNA damage.
The researchers also found that stem cells were more sensitive to this treatment:
“Compared with somatic cell types, embryonic stem cells and induced pluripotent stem cells displayed hypersensitivity to apoptotic induction by genotoxic agents.”
The chemotherapy doesn’t affect the healthy cells, says Nelson.
The team believes their discovery could help develop a strategy for making stem cell therapies safer for patients, while preserving their effectiveness. This would remove the barrier to using iPS cells in the clinic.
“Collectively, this study exploits a hypersensitive apoptotic response to DNA damage within pluripotent stem cells to decrease risk of dysregulated growth and augment the safety profile of transplant-ready, bioengineered progenitor cells,” they write.
This is an important step because more and more studies are showing that stem cells may be even more versatile than first thought: widening their potential to help patients with a greater variety of diseases, injuries and birth defects.
Researchers at the Mayo Clinic are putting a lot of effort into developing regenerative medicine using stem cells, as study co-author Andre Terzic, director of the Center for Regenerative Medicine at the Clinic, explains:
“By harnessing the potential of regenerative medicine, we’ll be able to provide more definitive solutions to patients.”
Written by Catharine Paddock PhD