[Trying to unravel an unresolved issue in regenerative medicine: gene expression profiling of MSCs].

BACKGROUND: Mesenchymal stem cells (MSCs) are adult fibroblastoid progenitor cells. Because of their immunoregulatory properties and their so-called trophic effects, MSCs play an important role in tissue regeneration, inflammation and trauma. Tissue trauma and challenge, for example during radiotherapy or infection, result in the release of so-called "danger molecules", which may be derived from dying cells or incoming pathogens. The molecular response of MSCs to this tissue stress remains largely elusive.

MATERIAL AND METHODS: In this study we examined the cell biological response of MSCs derived from human parotid glands (pgMSCs) and used bacterial endotoxin as a model of tissue stress and inflammation. PgMSCs from 3 donors were isolated, expanded and tested for classical tri-lineage plus myogenic differentiation. The cell biological response to the model "stressor" endotoxin was examined by low density gene expression arrays.

RESULTS: Through immunofluorescence and immunohistochemistry we were able to proof osteogenic, adipogenic, chondrogenic, and myogenic differentiation potential characteristic for stem cells. In vitro, gene expression analysis showed a characteristic modulation of MSCs after stimulation with endotoxin Lipopolysaccharide (LPS). Specifically, receptors and ligands typically involved in immune regulation, such as interleukins, TGF-β, tumor necrosis factors (TNF), and toll-like receptors (TLR), were regulated.

CONCLUSION: Our study elucidates some key functions and molecules, which are regulated in MSCs during tissue stress and inflammation. A thorough understanding of their cell biological function will aid future rationale therapeutic application of MSCs.