Molecular Composition Of Intercellular Contacts In Human Mesenchymal Stem Cells.

The long-term fate of stem cells depends on their interaction with the niche. Mesenchymal stem cells (MSC) from human bone marrow have been demonstrated to differentiate into various tissues, such as bone, cartilage, muscle and fat. As the interaction with the microenvironment plays a major role in differentiation, we have characterized the cell-cell contact among MSC. We have demonstrated the occurrence of a novel kind of adhering junction, consisting of slender, villiform-to-vermiform cell projections ( processus adhaerentes ). In this study, we have systematically analyzed the molecular composition of these junctions. A panel of antibodies specific for various components of tight junctions, gap junctions, adherens junctions and desmosomes was used. The expression of these antigens was verified by light and electron microscopy and by biochemical analysis, including immunoprecipitation and RT-PCR. MSC from two different sources were analyzed: MSC obtained from bone marrow aspirates from healthy voluntary donors and additionally MSC originating from umbilical cord blood donated for scientific research. We have also shown the presence of vimentin-positive retothelial cells (which are probably the source of MSC) in situ in fresh bone marrow samples. We demonstrate that MSC were interconnected by occasional gap junctions and frequent adhering junctions. Additionally, we found a unique molecular composition of these adhering junctions, as they comprise the transmembrane glycoproteins cadherin 11, N-cadherin and syndecan-1, together with the cytoplasmic plaque proteins α- and β-catenin and p120 ctn . Constitutive complexes of these molecules have been identified. Our data indicate that MSC communicate with each other through junctions and junctional complexes. We hypothesize that MSC can embark on alternative differentiation pathways with specific junctional and cytoskeletal patterns. Characterization of and understanding the role of such intercellular contacts and their correlation to specific differentiation programs are being conducted.