Researchers investigating the purported creation of 'STAP' cells have confirmed that the pluripotent cells were in fact derived from embryonic stem (ES) cells, and not by turning adult cells into a embryonic-like state by exposing them to stress, as was claimed.
The team, which included researchers from RIKEN's Center for Developmental Biology (CBD), says that whole-genome sequencing of STAP-related samples showed that the original cells had been contaminated with ES cells.
'Our investigations based on whole-genome sequencing of STAP cell-related materials reveal that all of these materials are derived from previously established ES cell lines and refute the evidence shown in the two Nature papers that cellular stress can reprogram differentiated cells into pluripotent cells,' they write.
It also says that 'chimeric mice and teratomas supposedly derived from STAP cells instead show ES cell contribution'. The findings were presented during RIKEN's own investigation, which concluded last year, but have now been published in a peer-reviewed journal.
Meanwhile, a group of researchers led by Harvard Medical School and Boston Children's Hospital has reported that attempts at replicating the production of STAP stem cells, including at the same lab that reported the creation of STAP cells, have failed.
'It's always impossible to prove the negative, but you can at least say – under the conditions that were reported – that these were neither robust nor reproducible in the hands of labs that should’ve been expert enough to do it,' said Professor George Daley of Harvard Medical School, who led the research.
All 133 attempts to produce STAP cells by seven teams of researchers across four countries failed, explains a Nature News editorial accompanying Professor Daley's report published in Nature – which also published the two original 'STAP' papers that were later retracted (see BioNews 757 and 761).
In January 2014, researchers at the CBD reported having created pluripotent STAP – stimulus-triggered acquisition of pluripotency – stem cells after exposure to stress, including exposure to acidic conditions (see BioNews 740).
The claim that mature cells could be reprogrammed into pluripotent STAP cells was questioned and then later retracted, however, as research teams quickly found controversies within the data and struggled to replicate the process with success (see BioNews 743 and 769).
Several members of the team at RIKEN have now resigned, and one of the co-authors, Professor Yoshiki Sasai, also former deputy director of the CBD, committed suicide in August 2014 (see BioNews 758 and 766).
Professor Daley described the efforts of teams across several countries to replicate STAP, including experiments undertaken in the laboratory where STAP first originated.
In one of the original studies, involving cells designed to express a fluorescent protein when pluripotency was indicated, some fluorescence was observed. Further testing showed this to be a false-positive, however – it was a natural phenomenon known as autofluoresence, as opposed to any sign of a transformation of the cells into the 'STAP-like' condition.
'To substantiate future claims of reprogramming and alternative states of potency, we urge a rigorous application of several independent means for validating functional pluripotency and genomic profiling to confirm cell-line provenance,' the team concluded.
The researchers warn that an 'essential standard of robustness and reproducibility must be met for new claims to exert a positive and lasting influence on the research community'.