Endothelial progenitor cell infusion induces hematopoietic stem cell reconstitution in vivo.
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.
Salter
Alice B
AB
Division of Cellular Therapy, Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Meadows
Sarah K
SK
Muramoto
Garrett G
GG
Himburg
Heather
H
Doan
Phuong
P
Daher
Pamela
P
Russell
Lauren
L
Chen
Benny
B
Chao
Nelson J
NJ
Chute
John P
JP
D000818:Animals; D001772:Blood Cell Count; D002454:Cell Differentiation / Q000502:physiology; D042783:Endothelial Cells / Q000502:physiology / Q000637:transplantation*; D005312:Fetal Blood / Q000166:cytology; D006410:Hematopoiesis / Q000502:physiology*; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology* / Q000528:radiation effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D020127:Recovery of Function; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000502:physiology; D014916:Whole-Body Irradiation / Q000009:adverse effects