Endothelial progenitor cell infusion induces hematopoietic stem cell reconstitution in vivo

Blood - Tập 113 - Trang 2104-2107 - 2009
Alice B. Salter1, Sarah K. Meadows1, Garrett G. Muramoto1, Heather Himburg1, Phuong Doan1, Pamela Daher1, Lauren Russell1, Benny Chen1, Nelson J. Chao1,2, John P. Chute1,3
1Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC
2Department of Immunology, Duke University, Durham, NC
3Department of Pharmacology and Cancer Biology, Duke University, Durham, NC

Tóm tắt

Hematopoietic stem cells (HSCs) reside in association with bone marrow (BM) sinusoidal vessels in vivo, but the function of BM endothelial cells (ECs) in regulating hematopoiesis is unclear. We hypothesized that hematopoietic regeneration following injury is regulated by BM ECs. BALB/c mice were treated with total body irradiation (TBI) and then infused with C57Bl6-derived endothelial progenitor cells (EPCs) to augment endogenous BM EC activity. TBI caused pronounced disruption of the BM vasculature, BM hypocellularity, ablation of HSCs, and pancytopenia in control mice, whereas irradiated, EPC-treated mice displayed accelerated recovery of BM sinusoidal vessels, BM cellularity, peripheral blood white blood cells (WBCs), neutrophils, and platelets, and a 4.4-fold increase in BM HSCs. Systemic administration of anti–VE-cadherin antibody significantly delayed hematologic recovery in both EPC-treated mice and irradiated, non–EPC-treated mice compared with irradiated controls. These data demonstrate that allogeneic EPC infusions can augment hematopoiesis and suggest a relationship between BM microvascular recovery and hematopoietic reconstitution in vivo.

Tài liệu tham khảo

Kaushansky, 2006, Lineage-specific hematopoietic growth factors., N Engl J Med, 354, 2034, 10.1056/NEJMra052706 Calvi, 2003, Osteoblastic cells regulate the haematopoietic stem cell niche., Nature, 425, 841, 10.1038/nature02040 Zhang, 2003, Identification of the haematopoietic stem cell niche and control of the niche size., Nature, 425, 836, 10.1038/nature02041 Arai, 2004, Tie2/angiopoietin-1 signaling regulates hematopoietic stem cell quiescence in the bone marrow niche., Cell, 118, 149, 10.1016/j.cell.2004.07.004 Kiel, 2005, SLAM family receptors distinguish hematopoietic stem and progenitor cells and reveal endothelial niches for stem cells., Cell, 121, 1109, 10.1016/j.cell.2005.05.026 Sacchetti, 2007, Self-renewing osteoprogenitors in bone marrow sinusoids can organize a hematopoietic microenvironment., Cell, 131, 324, 10.1016/j.cell.2007.08.025 Kiel, 2008, Uncertainty in the niches that maintain haematopoietic stem cells., Nat Rev Immunol, 8, 290, 10.1038/nri2279 Sugiyama, 2006, Maintenance of the hematopoietic stem cell pool by CXCL12-CXCR4 chemokine signaling in bone marrow stromal cell niches., Immunity, 25, 977, 10.1016/j.immuni.2006.10.016 Shalaby, 1995, Failure of blood-island formation and vasculogenesis in Flk-1-deficient mice., Nature, 376, 62, 10.1038/376062a0 Oberlin, 2002, Blood-forming potential of vascular endothelium in the human embryo., Development, 129, 4147, 10.1242/dev.129.17.4147 Chute, 2005, Soluble factors elaborated by human brain endothelial cells induce the concomitant expansion of purified human BM CD34+CD38- cells and SCID-repopulating cells., Blood, 105, 576, 10.1182/blood-2004-04-1467 Rafii, 1995, Human bone marrow microvascular endothelial cells support long-term proliferation and differentiation of myeloid and megakaryocytic progenitors., Blood, 86, 3353, 10.1182/blood.V86.9.3353.bloodjournal8693353 Chute, 2004, Ex vivo culture rescues hematopoietic stem cells with long-term repopulating capacity following harvest from lethally irradiated mice., Exp Hematol, 32, 308, 10.1016/j.exphem.2003.12.002 Chute, 2007, Transplantation of vascular endothelial cells mediates the hematopoietic recovery and survival of lethally irradiated mice., Blood, 109, 2365, 10.1182/blood-2006-05-022640 Kopp, 2005, Tie2 activation contributes to hemangiogenic regeneration after myelosuppression., Blood, 106, 505, 10.1182/blood-2004-11-4269 Chute, 2006, Inhibition of aldehyde dehydrogenase and retinoid signaling induces the expansion of human hematopoietic stem cells., Proc Natl Acad Sci U S A, 103, 11707, 10.1073/pnas.0603806103 Chen, 2002, A comparison of murine T-cell-depleted adult bone marrow and full-term fetal blood cells in hematopoietic engraftment and immune reconstitution., Blood, 99, 364, 10.1182/blood.V99.1.364 Yoder, 2007, Redefining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals., Blood, 109, 1801, 10.1182/blood-2006-08-043471 Gafter-Gvili, 2005, Meta-analysis: antibiotic prophylaxis reduces mortality in neutropenic patients., Ann Intern Med, 142, 979, 10.7326/0003-4819-142-12_Part_1-200506210-00008 May, 2005, Identification of a transiently exposed VE-cadherin epitope that allows for specific targeting of an antibody to the tumor neovasculature., Blood, 105, 4337, 10.1182/blood-2005-01-0010 Corada, 2001, Monoclonal antibodies directed to different regions of vascular endothelial cadherin extracellular domain affect adhesion and clustering of the protein and modulate endothelial permeability., Blood, 97, 1679, 10.1182/blood.V97.6.1679 Avecilla, 2004, Chemokine-mediated interaction of hematopoietic progenitors with the bone marrow vascular niche is required for thrombopoiesis., Nat Med, 10, 64, 10.1038/nm973