Stem Cell Antigen CD34 In Native And Engineered Form Alter Its Binding Ability To Stromal Cells And Ligands: A Classical Example Of Clinical Benefits Of Therapeutic Genetic Engineering Of Stem Cells In Transplantation

Abstract

CD34 is a highly glycosylated surface-expressed sialomucin and, because it is present on hematopoietic stem cells (HSCs), has demonstrated immense clinical utility in their enumeration in aphaeresis products, immunoaffinity purification for transplantation, and disease monitoring. The success of CD34 based reagents in identifying hematopoietic progenitors led to the assumption that CD34 is expressed on cells with regenerative potential and is sufficient for hematopoietic reconstitution in marrow-ablated recipients. However, its role has not been identified in substantial detail.With the advent of the fact that CD34 binds adapter protein like CRK-L in cytosol and CD34 knock out studies identified a a signaling role, CD34 antigen has been proposed to play a signaling function. Since it is a sialomucin, a member of the group adhesion molecules, we attempted to identify a role by over-expreesing its gene in cell lines. We report here that CD34 and engineered forms (Ser306 & Tyr318) significantly regulates adhesion to stromal cells, like mesenchymal stem cells and bone marrow ligands. These enhance binding of cells overexpressing CD34 by upregulating integrins and we therefore propose that such cells may effectively potentiate the success of transplantation through greater homing if they are used for transfusion.