Spontaneous in vitro transformation of human primary cells was, and continues to be, a scarcely described phenomenon. Only the description of the generation of the HaCAT cell line [1] is a canonical example, worldwide accepted. More recent examples included the emergence of tumorogenic populations upon in vitro culture of fetal human mesenchymal stem cells (hMSC), induced by GM-CSF and IL-4,[2] and bone marrow hMSC [3]. Other examples have also been reported after very long-term in vitro culture of telomerized hMSCTerT [4]. In this scenario, our previous results [5-7] were only a new observation to be added to this list. Only very recently similar results have been published [8], reporting spontaneous malignant transformation in 46% of bone marrow–derived hMSC long-term cultures (5–106 weeks). However, other authors reported opposite results [9].

Since our original publication, we continued to work on the definition and characterization of the hMSC spontaneous transformation phenomenon. Unexpectedly, however, we have been unable to obtain a single new human MSC transformation event (about 15 independent new adipose tissue samples–both adult and pediatric-, and 25 attempts of independent set of cultures). What we can, however, clearly state is that the ex vivo culture of human MSC under the conventional conditions promotes a variable but significant level of genomic instability, concurring with an important level of aneuploidy (Estrada et al., submitted). In any case, in all experiments, after a clear senescent phase the culture was exhausted. When we began to observe this central discrepancy we tried to evaluate several factors that could influence it, but finally, we carried out a STR (short tandem repeats) analysis to control the possibility of cross-contamination between the different TMC (for transformed mesenchymal stem cells) samples or between TMC and MSC cultures.