Differentiation Potential of Human Postnatal MSC, MAB and MAPC Reflected in their Transcriptome and Partially Influenced by the Culture Conditions

摘要

Several adherent postnatal stem cells have been described with different phenotypic and functional properties. As many of these cells are being considered for clinical therapies, it is of great importance that the identity and potency of these products is validated. We compared the phenotype and functional characteristics of human Mesenchymal Stem Cells (hMSC), Mesoangioblasts (hMab) and Multipotent Adult Progenitor Cells (hMAPC) using uniform standardized methods. Human MAPC could be expanded significantly longer in culture. Differences in cell surface marker expression were found among the three cell populations with CD140b being a distinctive marker among the three cell types. Differentiation capacity towards adipocytes, osteoblasts, chondrocytes and smooth muscle cells in vitro, using established protocols, was similar among the three cell types. However, only hMab differentiated to skeletal myocytes, while only hMAPC differentiated to endothelium in vitro and in vivo. A comparative transcriptome analysis confirmed that the three cell populations are distinct and revealed gene signatures that correlated with their specific functional properties. Furthermore, we assessed whether the phenotypic, functional and transcriptome features were mediated by the culture conditions. Human MSC and hMab cultured under MAPC conditions became capable of generating endothelial-like cells, whereas hMab lost some of their ability to generate myotubes. By contrast, hMAPC cultured under MSC conditions lost their endothelial differentiation capacity, while this was retained when cultured under Mab conditions, however myogenic capacity was not gained under Mab conditions. These studies demonstrate that hMSC, hMab and hMAPC have different properties that are partially mediated by the culture conditions.