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 Blood, 26 February 2009, Vol. 113, No. 9, pp. 2104-2107.
Prepublished online as a Blood First Edition Paper on January 13, 2009; DOI 10.1182/blood-2008-06-162941.

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TRANSPLANTATION

Brief report

Endothelial progenitor cell infusion induces hematopoietic stem cell reconstitution in vivo

Alice B. Salter1, Sarah K. Meadows1, Garrett G. Muramoto1, Heather Himburg1, Phuong Doan1, Pamela Daher1, Lauren Russell1, Benny Chen1, Nelson J. Chao1,2, and John P. Chute1,3

1 Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC; and 2 Department of Immunology and 3 Department of Pharmacology and Cancer Biology, Duke University, Durham, NC

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.


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