Osteogenic differentiation: a universal cell program of heterogeneous mesenchymal cells or a similar extracellular matrix mineralizing phenotype?

Despite the popularity of mesenchymal stem cells (MSCs), many fundamental aspects of their physiology still have not been understood. The information accumulated to date argues that MSCs from different sources vary in their differentiation potential and, probably, in molecular mechanisms of trilineage differentiation. Therefore, this review consists of two parts. Firstly, we focus on the data on inter- and intra-source variation of MSCs. We discuss in detail MSC variation at the single-cell level and direct omics comparison of MSCs from four main tissue sources: bone marrow, adipose tissue, umbilical cord and tooth. MSCs from all tissues represent heterogeneous populations in vivo with sub-populational structures reflecting their functional role in the tissue. After in vitro cultivation MSCs lose their natural heterogeneity, but obtain a new one, which might be regarded as a cultivation artifact. Nevertheless, MSCs from various sources still keep their functional differences after in vitro cultivation. In the second part of the review, we discuss how these differences influence molecular mechanisms of osteogenic differentiation. We highlight at least one subtype of mesenchymal cells differentiation with matrix mineralization — odontoblastic differentiation. We also discuss differences in molecular mechanisms of pathological heterotopic osteogenic differentiation of valve interstitial and tumor cells, but these assumptions need additional empirical confirmation. Finally, we observe differences in osteogenic differentiation molecular mechanisms of several MSC types and argue that this differentiation might be influenced by the cell context. Nevertheless, bone marrow and adipose MSCs seem to undergo osteogenic differentiation similarly, by the same mechanisms.