In 2007, after the University of Wisconsin’s James Thomson first created induced pluripotent stem (iPS) cells from human skin tissue, he told the New York Times that “by any means we test them they are the same as embryonic stem cells.” But over the past year or so, researchers have begun to realize that isn’t the case.

Several studies found that iPS cells often retain epigenetic signatures of the tissue they came from. A paper out in May reported that mice mounted an immune response to implanted iPS cells but not genetically identical embryonic stem cells. And most recently, researchers demonstrated that reprogrammed stem cells accumulate mutations in their mitochondrial DNA that were not present in the original cells.

A team led by James Adjaye from the Max Planck Institute for Molecular Genetics in Berlin sequenced the mitochondrial DNA of iPS cells derived from two separate lines of skin tissue using viral reprogramming. Reporting earlier this month in the journal Stem Cells, Adjaye’s team found that the two lines had around 20 and 80 point mutations each — more evidence of permanent genetic modification caused by the reprogramming process. In March, scientists reported in Nature that reprogramming to pluripotency also drives deletions and duplications of large stretches of genomic DNA.

“Genetic mutations in the mitochondrial genome may be responsible, for example, for various metabolic disorders, nervous diseases, tumours and post-transplant rejection reactions,” Adjaye wrote in a press release. “Therefore, it is essential that cell lines intended for clinical use be tested for such mutations.”