Adhesion of Human Hematopoietic Progenitor Cells to Mesenchymal Stromal Cells Involves CD44

Abstract

Background: Direct cell-cell contact between hematopoietic progenitor cells (HPC) and their cellular microenvironment is essential for maintenance of ‘stemness’. We have previously demonstrated that a feeder layer of human mesenchymal stromal cells (MSC) could provide a surrogate model as a niche for human HPC. Maintenance of long-term culture-initiating cells was significantly lower on fibroblasts. Methods: Adhesion of HPC to MSC was further analyzed using our recently described adhesion assay based on gravitational force upon inversion and in combination with specific antibodies against CD44. Results: Adhesion of KG1a and CD34+ cells was significantly reduced by administration of a monoclonal CD44 antibody and for KG1a to a greater extent than for CD34+ cells. Interaction of HPC and MSC was further analyzed by laser scanning confocal microscopy. CD44 was located on the uropod of CD34+ cells at the site of contact with MSC and both cell types were interwoven by a network of fibronectin. Conclusion: Various adhesion proteins, including CD44, are involved in the contact of human HPC and human MSC and further analysis of the relative significance and interaction of these proteins will be crucial for the understanding of the mechanism of this specific cell-cell interaction.

Expression of the melanoma cell adhesion molecule in human mesenchymal stromal cells regulates proliferation, differentiation, and maintenance of hematopoietic stem and progenitor cells

“…1,5,8,22,[34][35][36] Several groups have described the involvement of adhesion proteins such as N-cadherin, CD44, CD29, NCAM, or Notch, in mediating a direct interaction with the cellular microenvironment that enhances HSPC self-renewal. 1,4,[37][38][39][40][41] We found that MCAM overexpression in hMSC led to reduced CD29 expression. In line with our findings, Walenda et al reported that siRNA-mediated CD29 knockdown in hMSC resulted in enhanced numbers of more primitive HSPC after co-culture with these hMSC.…”

Exploring the Human Term Placenta as a Novel Source for Stem Cells and their Application in the Clinic

“…However, MSC have also been shown to be effective when sourced from other tissues including human placenta , umbilical cord (Bakhshi et al, 2008, Huang et al, 2007, Wang et al, 2004 and adipose tissue (Nakao et al, 2010). Recent papers have demonstrated that many of the specific cell-cell interactions between HSC and stromal cells are critical and may be essential for HSC regulation both in vivo (Steiner et al, 2009) and in vitro (Jing et al, 2010, Song et al, 2010, Wagner et al, 2008, Wagner et al, 2007, Wein et al, 2010. Indeed, a majority of studies have shown that cell-cell contact between HSC and MSC is essential for their ex vivo expansion.…”

Mesenchymal stem/progenitor cells promote the reconstitution of exogenous hematopoietic stem cells in Fancg−/− mice in vivo

“…52,53 Given the reduced support activity of Fancg Ϫ/Ϫ MSPCs to HSPCs, we hypothesized that loss of Fancg in MSPCs alters HSPC adhesion to these MSPCs which in turn leads to the defect in the supportive activity of MSPCs to HSPCs. To test the hypothesis, an in vitro adhesion assay was performed as described previously.…”