Secretome of Senescent Adipose-Derived Mesenchymal Stem Cells Negatively Regulates Angiogenesis
Autor: | Andrey Ratushnyy, Ludmila Buravkova, M. I. Ezdakova |
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Rok vydání: | 2020 |
Předmět: |
Adult
animal structures Angiogenesis Adipose tissue Neovascularization Physiologic Catalysis Chorioallantoic Membrane Article lcsh:Chemistry Inorganic Chemistry Neovascularization Paracrine signalling replicative senescence angiogenesis Cell Movement Paracrine Communication medicine Human Umbilical Vein Endothelial Cells Humans Physical and Theoretical Chemistry Angiogenic Proteins lcsh:QH301-705.5 Molecular Biology Spectroscopy Tissue homeostasis Cells Cultured Cellular Senescence Cell Proliferation Matrigel Chemistry Organic Chemistry Mesenchymal stem cell senescence-associated secretory phenotype (SASP) Mesenchymal Stem Cells General Medicine Middle Aged Computer Science Applications Cell biology adipose-derived mesenchymal stem cells (ASCs) Chorioallantoic membrane lcsh:Biology (General) lcsh:QD1-999 Female medicine.symptom |
Zdroj: | International Journal of Molecular Sciences Volume 21 Issue 5 International Journal of Molecular Sciences, Vol 21, Iss 5, p 1802 (2020) |
ISSN: | 1422-0067 |
Popis: | Nowadays, paracrine regulation is considered as a major tool of mesenchymal stem cell (MSC) involvement in tissue repair and renewal in adults. Aging results in alteration of tissue homeostasis including neovascularization. In this study, we examined the influence of replicative senescence on the angiogenic potential of adipose-derived MSCs (ASCs). Angiogenic activity of conditioned medium (CM) from senescent and &ldquo young&rdquo ASCs was evaluated in chorioallantoic membrane (CAM) assay in ovo using Japanese quail embryos. Also, the formation of capillary-like tubes by human umbilical vein endothelial cells (HUVECs) in 3D basement membrane matrix &lsquo &lsquo Matrigel&rsquo &rsquo and HUVEC migration capacity were analyzed. Multiplex, dot-blot and gene expression analysis were performed to characterize transcription and production of about 100 angiogenesis-associated proteins. The results point to decreased angiogenic potential of senescent ASC secretome in ovo. A number of angiogenesis-associated proteins demonstrated elevation in CM after long-term cultivation. Meanwhile, VEGF (key positive regulator of angiogenesis) did not change transcription level and concentration in CM. Increasing both pro- (FGF-2, uPA, IL-6, IL-8 etc.) and antiangiogenic (IL-4, IP-10, PF4, Activin A, DPPIV etc.) factors was observed. Some proangiogenic genes were downregulated (IGF1, MMP1, TGFB3, PDGFRB, PGF). Senescence-associated secretory phenotype (SASP) modifications after long-term cultivation lead to attenuation of angiogenic potential of ASC. |
Databáze: | OpenAIRE |
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