Neuropotency of Human Mesenchymal Stem Cell Cultures: Clonal Studies Reveal the Contribution of Cell Plasticity and Cell Contamination

Various studies have shown neuropotency of bone marrow-derived human mesenchymal stem cells (hMSC) based on the appearance of cells with neural phenotype before or after neural induction protocols. However, to date, it is unclear which mechanisms account for this observation. We hypothesized that neural phenotypes observed in hMSC cultures can be because of both intrinsic cell plasticity and contamination by cells of neural origin. Therefore, we characterized 38 clones from hMSC cultures by assessing their adipogenic/osteogenic potential with specific mesenchymal differentiation protocols, and their molecular neural phenotype by RT-PCR analysis before and after exposure to a defined neural stem cell (NSC) medium for 8 days (neural protocol). We found 33 clones with mesenchymal potential and 15 of them also showed a neural phenotype. As neural phenotypes were maintained during the neural protocol, this suggested neural cell plasticity in 39% of all clones through pluripotency. Importantly, we were able to induce neural phenotypes in 11 of mesenchymal clones applying the neural protocol, demonstrating neural cell plasticity in 29% of all clones through the mechanism of transdifferentiation. Finally, 2 of 5 nonmesenchymal clones (5% of all clones) displayed a neural phenotype indicating neural cell contamination of hMSC cultures. In conclusion, we found 2 different ways of neuropotency of hMSC cultures: cell plasticity and cell contamination.