Increased plasma EPO and MIP-1α are associated with recruitment of vascular progenitors but not CD34(+) cells in autologous peripheral blood stem cell grafts
Received 28 October 2008; received in revised form 5 February 2009; accepted 18 February 2009. published online 24 February 2009.
Objective
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.
Materials and Methods
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.
Results
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-α, 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 (<2.0×103/kg) and “high” graft VPCs (≥2.0×103/kg) and cytokine levels were compared between the groups. At baseline, increased levels of macrophage inflammatory protein-1α (MIP-1α) 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.
Conclusions
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-1α 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.
aSprott Centre for Stem Cell Research, Regenerative Medicine Program, Ottawa Health Research Institute, Ottawa, Canada
bStem Cell Processing Laboratory, Canadian Blood Services, Ottawa, Canada
cOntario Cancer Biomarkers Network, Toronto, Canada
dDivision of Hematology, Department of Medicine, University of Ottawa, Ottawa, Canada
eBlood and Marrow Transplant Program, Department of Medicine, University of Ottawa, Ottawa, Canada
Offprint requests to: David Allan, M.Sc., M.D., Hematology and Blood and Marrow Transplantation, The Ottawa Hospital, General Campus, 501 Smyth Road, Box 704, Ottawa, Ontario K1H 8L6 Canada
ABSTRACT