Molecular Characterization of Unique Junctional Complexes as Communication Pathways among Mesenchymal Stem Cells.

The interaction between stem cells and their niche is essential for the balance between self-renewal and differentiation. Mesenchymal stem cells (MSC) from bone marrow are able to differentiate into various tissues, such as bone, cartilage, muscle and fat. We have characterized the intercellular contacts among MSC and previously demonstrated the occurrence of a novel kind of adhering junction, consisting of villiform-to-vermiform cell projections (processus adhaerentes). The molecular compositions of these junctions have now been elucidated. Using a panel of antibodies specific for various components of tight, gap and adhering junctions (the latter comprising desmosomes and adhering junctions), we systematically analyzed the junctional complexes of MSC obtained from bone marrow aspirates from healthy voluntary donors and compared the data to bone marrow tissue in situ. Light and electron microscopy was used and several biochemical analyses were applied, including immunoprecipitation and RT-PCR. We could show that intercellular connections in MSC are realized in vitro by occasional gap junctions and frequent adhering junctions. Intercellular projections are noted, often deeply intruding into the neighbouring cell. These findings have been confirmed in situ in bone marrow biopsy material. Furthermore, we analyzed the molecular composition of these junctions and cell-projections. In most of them, we found the transmembrane glycoproteins cadherin 11 and N-cadherin, together with the cytoplasmic plaque proteins alpha- and beta-catenin and protein p120^ctn. Interestingly, similar junctions had been already noted in primary mesenchymal stem cells of day 7 to 8.5 mouse embryos. Our hypothesis is that this junction type might be a prerequisite for early mesenchymal cells. Our findings indicate that intercellular communication in MSC in human marrow is realized through a unique type of junctional complexes not described before. These structures are crucial for the long-term fate and differentiation of the cells and might have significant impact on the interaction with hematopoietic stem cells.