Endothelial-like vascular progenitor cells (VPCs) from allogeneic and autologous donors: mobilization features distinct from hematopoietic progenitors.
Endothelial-like progenitor cells circulate in the peripheral blood (PB) and can be enumerated using cell culture-based progenitor assays. These circulating vascular progenitor cells (VPCs) are implicated in new vessel formation and regenerative potential in several animal and human models of tissue injury. Given the emerging role of VPCs in regenerative processes and the limited information on the availability of such progenitor cells, we sought to determine baseline circulating VPC levels in healthy allogeneic donors and autologous hematopoietic transplant patients. VPC numbers were also measured in peripheral blood stem cell (PBSC) grafts from both graft types. Immunohistochemistry revealed that VPC clusters obtained under our culture conditions were CD45(+) and acquired endothelial features (CD31 and vascular endothelial-cadherin) in vitro upon angiogenic stimulation and gradually lost monocytic surface markers (CD14). Before PBSC mobilization, VPCs levels varied substantially in healthy donors and were markedly lower in patients with hematologic malignancies compared with healthy allogeneic donors with 27 +/- 15 versus 99 +/- 21 VPCs/mL (mean +/- SEM), respectively (P = .001). In patients undergoing stem cell mobilization, VPCs in the PB increased from 7 +/- 2 on day 0 to 51 +/- 9 by day 7 of mobilization (P = .05), representing a median fold increase of 8.9 (range, 3.0-29.8). Although autologous transplant patients underwent more intensive mobilization, VPCs were higher in allogeneic (7.2 +/- 1.4 x 10(3)/kg) than in autologous (2.6 +/- 1.5 x 10(3)/kg) mobilized PB grafts (P = .045). To identify predictors of VPC content, graft VPCs were compared with levels of CD34(+) cells, total colony forming unit (CFU), or granulocyte-macrophage colony forming unit (GM-CFU). None of these hematopoietic progenitors correlated with VPC numbers in PBSC grafts (P = NS). However, PB monocyte levels were highly correlated with circulating VPC levels (r = 0.71, P < .0001). Thus, our analysis identified significant variability in VPCs at baseline and in PBSC grafts from healthy donors. Nevertheless, these donors remain a better source of VPCs than do autologous transplant patients. Importantly, VPC mobilization occurs independently of hematopoietic mobilization. In view of the potential role of VPCs in recovery from transplant-related tissue injury, angiogenic mobilization strategies that complement hematopoietic mobilization will need to be specifically designed.
Allan
David S
DS
Division of Hematology-Oncology, Hopital Maisonneuve-Rosemont, and Department of Medicine, University of Montreal, Montreal, Quebec, Canada.
Dubé
Pascale
P
Roy
Jean
J
Busque
Lambert
L
Roy
Denis Claude
DC
D000328:Adult; D000368:Aged; D001772:Blood Cell Count; D018929:Cell Culture Techniques; D003114:Colony-Forming Units Assay; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D019650:Hematopoietic Stem Cell Mobilization; D006801:Humans; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation; D012016:Reference Values; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014182:Transplantation, Autologous; D014184:Transplantation, Homologous