Regulation of Adipose Tissue Stem Cells Angiogenic Potential by Tumor Necrosis Factor-Alpha

ABSTRACT Tissue regeneration requires coordinated “teamwork” of growth factors, proteases, progenitor and immune cells producing inflammatory cytokines. Mesenchymal stem cells (MSC) might play a pivotal role by substituting cells or by secretion of growth factors or cytokines, and attraction of prog...

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Published in:Journal of cellular biochemistry 2016-01, Vol.117 (1), p.180-196
Main Authors: Zubkova, Ekaterina S., Beloglazova, Irina B., Makarevich, Pavel I., Boldyreva, Maria A., Sukhareva, Olga Yu, Shestakova, Marina V., Dergilev, Konstantin V., Parfyonova, Yelena V., Menshikov, Mikhail Yu
Format: Article
Language:English
Subjects:
Actins - metabolism
Adipose Tissue - cytology
Adipose Tissue - metabolism
ADIPOSE-DERIVED STEM CELL
Adult
ANGIOGENESIS
Animals
Cell Cycle - drug effects
Cell Line
Cell Proliferation - drug effects
Cell Survival - drug effects
Cells, Cultured
Flow Cytometry
Humans
INFLAMMATION
Interleukin-6 - metabolism
Interleukin-8 - metabolism
Male
Mice
Middle Aged
REGENERATION
Stem Cells - cytology
Stem Cells - drug effects
Stem Cells - metabolism
TNF-α
Tumor Necrosis Factor-alpha - pharmacology
Young Adult
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Summary:ABSTRACT Tissue regeneration requires coordinated “teamwork” of growth factors, proteases, progenitor and immune cells producing inflammatory cytokines. Mesenchymal stem cells (MSC) might play a pivotal role by substituting cells or by secretion of growth factors or cytokines, and attraction of progenitor and inflammatory cells, which participate in initial stages of tissue repair. Due to obvious impact of inflammation on regeneration it seems promising to explore whether inflammatory factors could influence proangiogenic abilities of MSC. In this study we investigated effects of TNF‐α on activity of adipose‐derived stem cells (ADSC). We found that treatment with TNF‐α enhances ADSC proliferation, F‐actin microfilament assembly, increases cell motility and migration through extracellular matrix. Exposure of ADSC to TNF‐α led to increased mRNA expression of proangiogenic factors (FGF‐2, VEGF, IL‐8, and MCP‐1), inflammatory cytokines (IL‐1β, IL‐6), proteases (MMPs, uPA) and adhesion molecule ICAM‐1. At the protein level, VEGF, IL‐8, MCP‐1, and ICAM‐1 production was also up‐regulated. Pre‐incubation of ADSC with TNF‐α‐enhanced adhesion of monocytes to ADSC but suppressed adherence of ADSC to endothelial cells (HUVEC). Stimulation with TNF‐α triggers ROS generation and activates a number of key intracellular signaling mediators known to positively regulate angiogenesis (Akt, small GTPase Rac1, ERK1/2, and p38 MAP‐kinases). Pre‐treatment with TNF‐α‐enhanced ADSC ability to promote growth of microvessels in a fibrin gel assay and accelerate blood flow recovery, which was accompanied by increased arteriole density and reduction of necrosis in mouse hind limb ischemia model. These findings indicate that TNF‐α plays a role in activation of ADSC angiogenic and regenerative potential. J. Cell. Biochem. 117: 180–196, 2016. © 2015 Wiley Periodicals, Inc.
ISSN:0730-2312
1097-4644
DOI:10.1002/jcb.25263