title: Platelet-derived microparticles bind to hematopoietic stem/progenitor cells and enhance their engraftment.
abstract: Because human CD34+ and murine Sca-1+ hematopoietic stem-progenitor cells (HSPCs) express platelet-binding sialomucin P-selectin (CD162) and integrin Mac-1 (CD11b-CD18) antigen, it was inferred that these cells might interact with platelets. As a result of this interaction, microparticles derived from platelets (PMPs) may transfer many platelet antigens (CD41, CD61, CD62, CXCR4, PAR-1) to the surfaces of HSPCs. To determine the biologic significance of the presence of PMPs on human CD34+ and murine Sca-1+ cells, their expressions on mobilized peripheral blood (mPB) and on nonmobilized 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. Finally, the hematopoietic reconstitution of lethally irradiated mice receiving transplanted BM mononuclear cells covered or not covered with PMPs was examined. 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 increase adhesion of these cells to endothelium and immobilized SDF-1. Moreover, murine BM cells covered with PMPs engrafted lethally irradiated mice significantly faster than those not covered, indicating that PMPs play an important role in the homing of HSPCs. This could explain why in a clinical setting human mPB HSPCs (densely covered with PMPs) engraft more rapidly than BM HSPCs (covered with fewer PMPs). These findings indicate a new role for PMPs in stem cell transplantation and may have clinical implications for the optimization of transplantations.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
authors.forename: A
authors.initials: A
authors.lastname: Janowska-Wieczorek
authors.forename: M
authors.initials: M
authors.lastname: Majka
authors.forename: J
authors.initials: J
authors.lastname: Kijowski
authors.forename: M
authors.initials: M
authors.lastname: Baj-Krzyworzeka
authors.forename: R
authors.initials: R
authors.lastname: Reca
authors.forename: A R
authors.initials: AR
authors.lastname: Turner
authors.forename: J
authors.initials: J
authors.lastname: Ratajczak
authors.forename: S G
authors.initials: SG
authors.lastname: Emerson
authors.forename: M A
authors.initials: MA
authors.lastname: Kowalska
authors.forename: M Z
authors.initials: MZ
authors.lastname: Ratajczak
mesh_terms: D000818:Animals; D018952:Antigens, CD34 / Q000032:analysis; D016824:Antigens, Human Platelet / Q000378:metabolism; D000950:Antigens, Ly / Q000032:analysis; D001792:Blood Platelets / Q000378:metabolism* / Q000648:ultrastructure; D001854:Bone Marrow Cells / Q000378:metabolism; D002448:Cell Adhesion; D002455:Cell Division; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000378:metabolism; D003114:Colony-Forming Units Assay; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005260:Female; D006085:Graft Survival; D018922:HL-60 Cells; D019650:Hematopoietic Stem Cell Mobilization; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D008562:Membrane Glycoproteins / Q000032:analysis; D008565:Membrane Proteins / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D015539:Platelet Activation; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000378:metabolism; D011828:Radiation Chimera; D013997:Time Factors; D014471:Umbilical Veins
chemical_list: D018952:Antigens, CD34; D016824:Antigens, Human Platelet; D000950:Antigens, Ly; C515255:CXCL12 protein, human; D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; C074650:Ly6a protein, mouse; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; C084882:P-selectin ligand protein; D019039:Platelet Glycoprotein GPIIb-IIIa Complex