Elsevier

Stem Cell Research

Volume 6, Issue 3, May 2011, Pages 238-250
Stem Cell Research

Regular Article
Density of human bone marrow stromal cells regulates commitment to vascular lineages

https://doi.org/10.1016/j.scr.2011.02.001Get rights and content
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Abstract

Mechanisms underlying the vascular differentiation of human bone marrow stromal cells (HBMSCs) and their contribution to neovascularisation are poorly understood. We report the essential role of cell density-induced signals in directing HBMSCs along endothelial or smooth muscle lineages. Plating HBMSCs at high density rapidly induced Notch signaling, which initiated HBMSC commitment to a vascular progenitor cell population expressing markers for both vascular lineages. Notch also induced VEGF-A, which inhibited vascular smooth muscle commitment while consolidating differentiation to endothelial cells with cobblestone morphology and characteristic endothelial markers and functions. These mechanisms can be exploited therapeutically to regulate HBMSCs during neovascularisation.

Abbreviations

αSMA
smooth muscle alpha actin
DAPT
N-[N-(3,5-difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester
DMSO
dimethyl sulfoxide
ECs
endothelial cells
EDTA
ethylenediaminetetraacetic acid
HES-1
hairy enhancer of split-1
HUVECs
human umbilical vein endothelial cells
LDL
low density lipoprotein
HBMSCs
human bone marrow stromal cells
PECAM-1
platelet endothelial cell adhesion molecule-1 (CD31)
SM-MHC-1
vascular smooth muscle myosin heavy chain 1
VCAM-1
vascular cell adhesion molecule
VE-cadherin
vascular endothelial cadherin
VEGF
vascular endothelial growth factor
VEGFR1
vascular endothelial growth factor receptor 1
VEGF-I
VEGF neutralization antibody
VEGFR-I
VEGFR signaling inhibitor
vSMC
vascular smooth muscle cell
vWF
Von Willebrand factor.

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