Increased plasma EPO and MIP-1α are associated with recruitment of vascular progenitors but not CD34(+) cells in autologous peripheral blood stem cell grafts

Abstract

Increased levels of endothelial-like vascular progenitor cells (VPCs) in peripheral blood stem cell (PBSC) products have been associated with reduced transplant-related toxicity following autologous hematopoietic stem cell transplantation. In this study, a panel of angiogenic and inflammatory plasma proteins were quantitatively analyzed in patients undergoing PBSC collection for autologous hematopoietic stem cell transplantation to identify profiles associated with greater VPC recruitment. A panel of 16 candidate plasma factors were quantified using multianalyte fluorescence and/or enzyme-linked immunosorbent assay. VPC clusters were enumerated using a standard cell culture assay. Thirty-six patients (mean age=51 years, 42% female) had plasma collected at baseline prior to PBSC mobilization and on the day of PBSC collection. Only erythropoietin (EPO) levels increased significantly on the day of PBSC collection in comparison with baseline plasma levels (2.2-fold increase; p=0.003). Interleukin-2, -10, epidermal growth factor, interferon-alpha, and angiopoietin-1 all decreased significantly between baseline and the day of PBSC collection (p<0.02). The remaining cytokine levels did not change appreciably (p=NS). The cohort was divided into "low" graft VPCs (<2.0 x 10(3)/kg) and "high" graft VPCs (>or=2.0 x 10(3)/kg) and cytokine levels were compared between the groups. At baseline, increased levels of macrophage inflammatory protein-1 alpha (MIP-1 alpha) were associated with increased graft VPCs (p=0.05) while higher EPO concentrations on the day of PBSC collection predicted higher graft VPC levels (p=0.02). These cytokines were not associated with CD34(+) cell mobilization. The association of different plasma proteins with graft VPC and CD34(+)-cell levels suggests that mobilization of vascular and hematopoietic progenitors occurs through independent mechanisms. Patients with low levels of MIP-1 alpha at baseline may be candidates for interventions aimed at increasing graft VPC levels. Strategies that increase plasma EPO concentrations may be most promising to augment the regenerative properties of PBSC products.