Mesenchymal stem cells (MSCs) have generated a great deal of excitement and expectation as a potential source of cells for cell-based therapeutic strategies, primarily because of their intrinsic ability to self-renew and differentiate into functional cell types that constitute the tissue in which they exist . Despite diverse and ever-growing information concerning MSCs and their use in clinical strategies, the mechanisms that govern MSC self-renewal and multilineage differentiation are not well understood and remain an active area of investigation . Therefore, research efforts focused on identifying factors that regulate and control MSC fate decisions become crucial in the promotion of a greater understanding of the molecular, biological, and physiological characteristics of this potentially highly useful stem cell type . Despite the fact that the pioneering experimental evidence supports the existence of bone marrow–derived MSCs , MSCs have up to now, been isolated from other tissue sources, suggesting that MSCs are diversely distributed in vivo and may occupy an ubiquitous stem cell niche . The heterogeneity of MSCs, demonstrated in both in vivo and in vitro studies , with respect to their self-renewal and differentiation potentials, can be explained by the notion that the MSC pool comprises not only putative “mesenchymal stem cells” but also subpopulations at different states of differentiation (e.g., quadra-, tri-, bi-, and unipotential MSCs) . Depending on the specific culture conditions and stimuli used, MSCs are able to form bone, cartilage, tendon, muscle, fat, and neural tissue as well as hematopoietic-supporting stroma . MSCs can also be transdifferentiated by specific transcriptional activators, even though it is not understood what specific environmental cues are necessary to initiate their proliferation and differentiation, producing autocrine and paracrine factors essential for lineage progression [1, 6]. Despite increasing biomolecular and morphologic knowledge of MSCs, an understanding of the full functional differentiation capacity of MSCs, the mechanisms controlling their mobilization and their homing properties, their differentiation program to various tissue types, and their physiological role are needed. In this respect, several studies have provided evidence on the importance of the expression and production of both adhesion molecules and extracellular matrix (ECM) components [2, 3], which contribute to the formation and function of a unique microenvironment that produces induction-regulating signals [6, 7]. Many adhesion molecules and ECM proteins identified in MSCs are regulated/activated and made biologically functional through proteolysis by matrix metalloproteinases (MMPs), endopeptidases belonging to the family of matrixins that are able to regulate several physiological processes . The interaction between MMP proteolytic activity and the multifaceted functions of tissue inhibitors of metalloproteinases (TIMPs) are biologically crucial for many developmental events , including morphogenesis, cell proliferation, and apoptosis [10, 11], as well as tissue development, through the modulation of biologically active molecules [12, 13].
Recently, biomolecular studies highlighted, in MSCs, the gene expression involved in the connection between cell-matrix and cell-cell external signals, as well as in the intracellular signalling pathways. In fact, MMP [14–16] and TIMP [14, 15] genes have been identified in MSCs derived from different biological sources, indicating both their common ontogeny and the activation of similar sets of genes because of their close functional roles. Their gene-expression profiles, as part of the transcriptome of MSCs, may provide possible explanations for MSC functioning and behavior.