Novel aspects of parenchymal–mesenchymal interactions: from cell types to molecules and beyond

Abstract

Mesenchymal stem or stromal cells (MSCs) were initially isolated from the bone marrow and received their name on the basis of their ability to differentiate into multiple lineages such as bone, cartilage, fat and muscle. However, more recent studies suggest that MSCs residing in perivascular compartments of the small and large blood vessels play a regulatory function supporting physiologic and pathologic responses of parenchymal cells, which define the functional representation of an organ or tissue. MSCs secrete or express factors that reach neighbouring parenchymal cells via either a paracrine effect or a direct cell-to-cell interaction promoting functional activity, survival and proliferation of the parenchymal cells. Previous concept of 'epithelial-stromal' interactions can now be widened. Given that MSC can also support hematopoietic, neuronal and other non-epithelial parenchymal lineages, terms 'parenchymal-stromal' or 'parenchymal-mesenchymal' interactions may better describe the supportive or 'trophic' functions of MSC. Importantly, in many cases, MSCs specifically provide supportive microenvironment for the most primitive stem or progenitor populations and therefore can play a role as 'stem/progenitor niche' forming cells. So far, regulatory roles of MSCs have been reported in many tissues. In this review article, we summarize the latest studies that focused on the supportive function of MSC. This thread of research leads to a new perspective on the interactions between parenchymal and mesenchymal cells and justifies a principally novel approach for regenerative medicine based on co-application of MSC and parenchymal cell for the most efficient tissue repair.

Paracrine effects of stem cells in wound healing and cancer progression

“…Strongly attracted to wounds, MSCs are mobilized by injuries which they enter to modulate inflammatory responses and stimulate tissue regeneration (10). MSCs are a heterogeneous population and can also emerge from pericytes or endothelial cells (11), which may help to accelerate local MSC recruitment. MSCs were originally reported to contribute to tissue repair by trans-differentiating into cells, such as epithelial cells or neurons, that are required to restore the injured tissue (12–15).…”

“…MSCs were originally reported to contribute to tissue repair by trans-differentiating into cells, such as epithelial cells or neurons, that are required to restore the injured tissue (12–15). However, later it became evident that their paracrine activities are more important for wound healing than their differentiation potential (11,16,17). …”

Lysophosphatidic acid mediates fibrosis in injured joints by regulating collagen type I biosynthesis

“…Reducing excessive COL I deposition and fibrocartilage formation via the selective blockade of ATX and/or LPA receptors or downstream targets of LPA signaling may significantly improve the quality of cartilage tissue formed after microfracture surgery. Previously published data suggest that paracrine interaction between chondrocytes and BMSCs may also enhance cartilage regeneration via trophic/supportive effect of BMSCs 36–38 and it is interesting to speculate that reduction of fibrosis may indirectly contribute to this paracrine crosstalk.…”

Mesenchymal Stem Cells Manage Endogenous Tissue Regeneration

“…(1,19) Firmly attracted to wounds, MSCs are mobilized by injuries which they enter to modulate inflammatory responses and stimulate tissue regeneration. (20) MSCs are a heterogeneous population and also able to emerge from pericytes or endothelial cells (21), which may help to accelerate local MSC recruitment. MSCs were originally known to have role in tissue repair by trans-differentiating into cells, such as epithelial cells or neurons, which are required to restore the injured tissue.…”

“…(22)(23)(24)(25) However, later it became evident that their paracrine activities are more important for wound healing than their differentiation potential. (21,(26)(27)(28) It is important to understand that all adult stem cell systems exist to guarantee that when cells within tissues expire naturally, these cells can be expeditiously replaced to provide physiological balance in the organism. Every cell in the body has a lifespan ranging from 20 minutes to many years depending on the cell.…”