title: 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 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.
authors.affiliation: Russian Cardiology Research and Production Complex, Moscow, Russian Federation.
authors.forename: Ekaterina S
authors.initials: ES
authors.lastname: Zubkova
authors.affiliation: Russian Cardiology Research and Production Complex, Moscow, Russian Federation.
authors.forename: Irina B
authors.initials: IB
authors.lastname: Beloglazova
authors.affiliation: Russian Cardiology Research and Production Complex, Moscow, Russian Federation.|Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation.
authors.forename: Pavel I
authors.initials: PI
authors.lastname: Makarevich
authors.affiliation: Russian Cardiology Research and Production Complex, Moscow, Russian Federation.
authors.forename: Maria A
authors.initials: MA
authors.lastname: Boldyreva
authors.affiliation: Endocrinology Research Centre, Moscow, Russian Federation.
authors.forename: Olga Yu
authors.initials: OY
authors.lastname: Sukhareva
authors.affiliation: Endocrinology Research Centre, Moscow, Russian Federation.|I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation.
authors.forename: Marina V
authors.initials: MV
authors.lastname: Shestakova
authors.affiliation: Russian Cardiology Research and Production Complex, Moscow, Russian Federation.
authors.forename: Konstantin V
authors.initials: KV
authors.lastname: Dergilev
authors.affiliation: Russian Cardiology Research and Production Complex, Moscow, Russian Federation.|Faculty of Medicine, Lomonosov Moscow State University, Moscow, Russian Federation.
authors.forename: Yelena V
authors.initials: YV
authors.lastname: Parfyonova
authors.affiliation: Russian Cardiology Research and Production Complex, Moscow, Russian Federation.
authors.forename: Mikhail Yu
authors.initials: MY
authors.lastname: Menshikov
mesh_terms: D000199:Actins / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology* / Q000378:metabolism; D000328:Adult; D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D051379:Mice; D008875:Middle Aged; D013234:Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000199:Actins; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha
keywords: ADIPOSE-DERIVED STEM CELL; ANGIOGENESIS; INFLAMMATION; REGENERATION; TNF-α