Characterization of Intercellular Junctional Complexes between Human Hematopoietic and Mesenchymal Stem Cells.

The interaction between hematopoietic stem cells and their niche is essential for the balance between self-renewal and differentiation. We previously demonstrated that intercellular connections in mesenchymal stem cells (MSC) are realized by occasional gap junctions and frequent adherens junctions, comprising specific cadherin-catenin-complexes. Using MSC-feeder-layer as a surrogate model for the hematopoietic stem cell (HSC) niche, we have analyzed the intercellular junctional complexes between HSC and MSC.

MSC were obtained from bone marrow aspirates from healthy voluntary donors. HSC were isolated from umbilical cord blood. Using advanced confocal laser scanning in combination with deconvolution and volume rendering software, we were able to produce 3D-images of intercellular junctions between HSC and MSC. We used a panel of antibodies specific for various components of tight, gap and adherens junctions. Additionally, we compared the data to human and bovine bone marrow tissue in situ.

We could show that intercellular connections between HSC and MSC are mainly realized by podia formation of the HSC linking to the adjacent MSC. These podia vary greatly in length and shape (uropodia, filopodia). Along these podia and especially at the contact zone to the MSC, we have identified the cytoplasmic plaque proteins alpha- and beta-catenin and protein p120^ctn, as well as the transmembrane glycoprotein N-cadherin.

This study provided solid evidence for the direct and intimate cellular interaction of HSCs with their niche. Direct cell contact represents a key factor for the regulation of self-renewal versus differentiation. The examination of the specific function of catenins, p120^ctn and N-cadherin in this process is concurrently underway.