What Molecular Recognition Systems Do Mesenchymal Stem Cells/Medicinal Signaling Cells (MSC) Use to Facilitate Cell-Cell and Cell Matrix Interactions? A Review of Evidence and Options

Abstract

Mesenchymal stem cells, also called medicinal signaling cells (MSC), have been studied regarding their potential to facilitate tissue repair for >30 years. Such cells, derived from multiple tissues and species, are capable of differentiation to a number of lineages (chondrocytes, adipocytes, bone cells). However, MSC are believed to be quite heterogeneous with regard to several characteristics, and the large number of studies performed thus far have met with limited or restricted success. Thus, there is more to understand about these cells, including the molecular recognition systems that are used by these cells to perform their functions, to enhance the realization of their potential to effect tissue repair. This perspective article reviews what is known regarding the recognition systems available to MSC, the possible systems that could be looked for, and alternatives to enhance their localization to specific injury sites and increase their subsequent facilitation of tissue repair. MSC are reported to express recognition molecules of the integrin family. However, there are a number of other recognition molecules that also could be involved such as lectins, inducible lectins, or even a MSC-specific family of molecules unique to these cells. Finally, it may be possible to engineer expression of recognition molecules on the surface of MSC to enhance their function in vivo artificially. Thus, improved understanding of recognition molecules on MSC could further their success in fostering tissue repair.

One of the Primary Functions of Tissue-Resident Pluripotent Pericytes Cells May Be to Regulate Normal Organ Growth and Maturation: Implications for Attempts to Repair Tissues Later in Life

“…It is clear that much of the literature regarding the use of pluripotent cells for tissue engineering and other applications of free cells has been with older populations where tissues and organs have been damaged by the aging process and disease. Many of these issues have been reviewed recently by Hart [ 51 ]. Such approaches for the repair and regeneration of tissues/organs damaged by disease are complicated by the presence of an inflammation that can compromise the functionality of the cells [ 88 , 103 ] or the effectiveness of the effort [ 110 ].…”

“…Obviously, it would be important to better understand the limitations of such approaches and develop methods to overcome these limitations in a tissue/organ-specific manner. Thirdly, little is known regarding the recognition systems that these pluripotent progenitor cells use to localize and associate with the ECM and other cells in a tissue [ 51 ]. That is, how can one use endogenous recognition molecules to enhance localization to specific sites, or failing that, can one enhance localization and incorporation at a site via engineered surface molecules [ 51 ].…”

“…Specificity may be manifested via the glycolytic linkages in glycoproteins or on cells [ 7 , 50 ]. Such an organ-specific ECM could contribute to the localization of the cells in the organ via cell receptors as has been reviewed recently by Hart [ 51 ], as a source of biologically active molecules bound to the elements of the ECM, such as in bone [ 52 ], as an example, and contribute to the morphology of specific organs [ 53 ]. Furthermore, the ECM in an organ is likely dynamic and can be altered by injury or during the aging process [ 54 , 55 ], factors that could impact organ integrity and functioning.…”

Perspective: Is It Time to Rename MSC (Mesenchymal Stem Cells/Medicinal Signaling Cells) with a Name that Reflects Their Combined <i> In Vivo </i> Functions and Their <i> In Vitro </i>Abilities?—Possibly “Pluripotent Mesenchymal Regulatory Cells (PMRC)”

“…While some of this lack of localization is likely due to a lack of understanding of what recognition systems "MSC" use and how they are regulated [7], even when the recognition systems are augmented artificially there is improvement but it still does not lead to consistent large scale localization and differentiation [7]. Further studies have focused on the localization of "MSC" in tissues as pericytes that can release molecules and apparently, actively release exosomes containing mediators and regulatory molecules that can act in a paracrine manner [22,23].…”

“…It has been noted that MSC from most tissues or fluids are very heterogeneous [5][6][7][8], and some cells appear to have unique epigenetic signatures [9][10][11], as well as carbohydrate signatures as characterized by lectins [7,12]. Interestingly, MSC from bone marrow appear to preferentially respond to osteogenic stimuli, while MSC from synovium respond well to chondrogenic stimuli [5] in a pig model and thus, different locations may reflect the needs of such different biological and biomechanical environments.…”