Abstract :
[en] Background: In contrast to pluripotent embryonic stem cells, adult stem cells have been considered to be
multipotent, being somewhat more restricted in their differentiation capacity and only giving rise to cell types
related to their tissue of origin. Several studies, however, have reported that bone marrow-derived mesenchymal
stromal cells (MSCs) are capable of transdifferentiating to neural cell types, effectively crossing normal lineage
restriction boundaries. Such reports have been based on the detection of neural-related proteins by the
differentiated MSCs. In order to assess the potential of human adult MSCs to undergo true differentiation to a
neural lineage and to determine the degree of homogeneity between donor samples, we have used RT-PCR and
immunocytochemistry to investigate the basal expression of a range of neural related mRNAs and proteins in
populations of non-differentiated MSCs obtained from 4 donors.
Results: The expression analysis revealed that several of the commonly used marker genes from other studies
like nestin, Enolase2 and microtubule associated protein 1b (MAP1b) are already expressed by undifferentiated
human MSCs. Furthermore, mRNA for some of the neural-related transcription factors, e.g. Engrailed-1 and
Nurr1 were also strongly expressed. However, several other neural-related mRNAs (e.g. DRD2, enolase2, NFL
and MBP) could be identified, but not in all donor samples. Similarly, synaptic vesicle-related mRNA, STX1A could
only be detected in 2 of the 4 undifferentiated donor hMSC samples. More significantly, each donor sample
revealed a unique expression pattern, demonstrating a significant variation of marker expression.
Conclusion: The present study highlights the existence of an inter-donor variability of expression of neuralrelated
markers in human MSC samples that has not previously been described. This donor-related heterogeneity
might influence the reproducibility of transdifferentiation protocols as well as contributing to the ongoing
controversy about differentiation capacities of MSCs. Therefore, further studies need to consider the differences
between donor samples prior to any treatment as well as the possibility of harvesting donor cells that may be
inappropriate for transplantation strategies.
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