Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment

Because human CD34(+) and murine Sca-1(+) hematopoietic stem-progenitor cel ls (HSPCs) express platelet-binding sialomucin P-selectin (CD162) and integ rin Mac-1 (CD11b-CD18) antigen, it was inferred that these cells might inte ract with platelets. As a result of this interaction, microparticles derive d from platelets (PMPs) may transfer many platelet antigens (CD41, CD61, CD 62, CXCR4, PAR-1) to the surfaces of HSPCs. To determine the biologic signi ficance of the presence of PMPs on human CD34(+) and murine Sca-1(+) cells, their expressions on mobilized peripheral blood (mPB) and on non-mobilized PB- and bone marrow (BM)derived CD34(+) cells were compared. In addition, the effects of PMPs on the proliferation of CD34(+) and Sca-1(+) cells and on adhesion of HSPCs to endothelium and immobilized SDF-1 were studied. Fin ally, the hematopoietic reconstitution of lethally irradiated mice receivin g transplanted ISM mononuclear cells covered or not covered with PMPs was e xamined. It was found that PMPs are more numerous on mPB than on BM CD34(+) cells, do not affect the clonogenicity of human and murine HSPCs, and incr ease adhesion of these cells to endothelium and immobilized SDF-1. Moreover , Murine BM cells covered with PMPs engrafted lethally irradiated mice sign ificantly faster than those not covered, indicating that PMPs play an impor tant role in the homing of HSPCs. This could explain why in a clinical sett ing human mPB HSPCs (densely covered with PMPs) engraft more rapidly than B M HSPCs (covered with fewer PMPs). These findings indicate a new role for P MPs in stem cell transplantation and may have clinical implications for the optimization of transplantations. (C) 2001 by The American Society of Hema tology.