Proteomic definitions of mesenchymal stem cells

Abstract

Mesenchymal stem cells (MSCs) are pluripotent cells isolated from the bone marrow and various other organs. They are able to proliferate and self-renew, as well as to give rise to progeny of at least the osteogenic, chondrogenic, and adipogenic lineages. Despite this functional definition, MSCs can also be defined by their expression of a distinct set of cell surface markers. In the current paper, studies investigating the proteome of human MSCs are reviewed with the aim to identify common protein markers of MSCs. The proteomic analysis of MSCs revealed a distinct set of proteins representing the basic molecular inventory, including proteins for (i) cell surface markers, (ii) the responsiveness to growth factors, (iii) the reuse of developmental signaling cascades in adult stem cells, (iv) the interaction with molecules of the extracellular matrix, (v) the expression of genes regulating transcription and translation, (vi) the control of the cell number, and (vii) the protection against cellular stress.

Figure 1

Scientific publications in PubMed about MSCs. The PubMed database was searched for the terms “mesenchymal stem cell,” “mesenchymal stromal cell,” and “MSC” for the years 1990–2009. The emerging interest in MSCs is seen by the increasing number of publications.

Figure 2

Expression of cell surface markers of MSCs. Hierarchical clustering of the expression of cell surface markers of MSCs from different MSCs preparations. Cells were termed “mesenchymal stem cells (MSCs)" [11], “mesodermal progenitor cells (MPCs)" [12], “marrow-isolated adult multilineage inducible (MIAMI) cells" [13], and “bone marrow-isolated mesenchymal stem cells (BM-MSCs)," “adipose tissue-isolated stem cells (ADSCs)," “synovia-derived stem cells (SynoSCs)," “umbilical vein stem cells (UVSCs)," and “human embryonic stem cells (hESCs)" [14]. The figure shows the different cell preparations in columns and the surface antigens in rows. The green color codes for positive expression, yellow codes for low expression, red codes for no expression, and grey color stands for not determined in the respective experiments. It is seen that the cells can be defined by the presence and absence of a distinct pattern of cell surface markers, that is, CD34(−), CD45(−), CD117(−) (cKit), CD44(+), CD90(+), and CD166(+).

Figure 3

Comparison of 2DE gels of BM-MSCs and UCB-MSCs. This figure shows representative 2D gel images of (a) bone marrow (BM-)MSC proteins and (b) umbilical cord blood (UCB-)MSC proteins. (c) The false-colored overlay image of the two 2D gels shows the BM-MSC proteins colored in red, and the UCB-MSC proteins colored in green. The resulting overlaid color is yellow (data from [30, 47]). The overlaid gel images show a close relationship between the two cellular proteomes, but there seem to be more proteins in the BM-MSC group as well as some differences in protein expression, as seen in the unique color in one of the gels.

Figure 4

Proteomic definition of MSCs—proposal for the protein inventory. The main aspects for a proteomic definition of MSCs include (i) the expression of a specific cell surface markers, (ii) the reactiveness to growth factors, (iii) the re-activation of developmental pathways, (iv) the interaction with the extracellular matrix, (v) the regulation of transcription and translation, (vi) the regulation of cell number, and (vii) the machinery for resistance to cellular stress (modified from [6, 51]).