The DOI matches its Crossref record; 42 of the 42 references it cites were found in a registry or an index.
Tumor necrosis factor-α-activated mesenchymal stem cells promote endothelial progenitor cell homing and angiogenesis
Open accessAbstract
Mesenchymal stem cells (MSCs) accelerate regeneration of ischemic or injured tissues by stimulation of angiogenesis through a paracrine mechanism. Tumor necrosis factor-α (TNF-α)-activated MSCs secrete pro-angiogenic cytokines, including IL-6 and IL-8. In the present study, using an ischemic hindlimb animal model, we explored the role of IL-6 and IL-8 in the paracrine stimulation of angiogenesis and tissue regeneration by TNF-α-activated MSCs. Intramuscular injection of conditioned medium derived from TNF-α-treated MSCs (TNF-α CM) into the ischemic hindlimb resulted in attenuated severe limb loss and stimulated blood perfusion and angiogenesis in the ischemic limb. Immunodepletion of IL-6 and IL-8 resulted in attenuated TNF-α CM-stimulated tissue repair, blood perfusion, and angiogenesis. In addition, TNF-α CM induced migration of human cord blood-derived endothelial progenitor cells (EPCs) through IL-6- and IL-8-dependent mechanisms in vitro. Intramuscular injection of TNF-α CM into the ischemic limb led to augmented homing of tail vein-injected EPCs into the ischemic limb in vivo and immunodepletion of IL-6 or IL-8 from TNF-α CM attenuated TNF-α CM-stimulated homing of EPCs. In addition, intramuscular injection of recombinant IL-6 and IL-8 proteins resulted in increased homing of intravenously transplanted EPCs into the ischemic limb and improved blood perfusion in vivo. These results suggest that TNF-α CM stimulates angiogenesis and tissue repair through an increase in homing of EPCs through paracrine mechanisms involving IL-6 and IL-8.
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“Additionally, several cytokines produced by inflammatory cells have angiogenic effects, including TNF, IL-6, and IL-8 (57, 58).”
From The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis. (2017) · cites this paper as [57]
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Metadata
- Authors
- Kwon, Y. W., Heo, S. C., Jeong, G. O., Yoon, J. W., Mo, W. M., Lee, M. J., Jang, I.-H., Kwon, S. M., Lee, J. S., & Kim, J. H.
- Affiliations
- Pusan National University (KR)
- Pusan National University Yangsan Hospital (KR)
- Corresponding author
- Kim, Jae Ho
- Venue
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 1832
- Issue
- 12
- Pages
- 2136-2144
- ISSN
- 0925-4439 (ISSN-L)
- OpenAlex
- W1968254493
- Cited by
- 137
- References
- 42
- Citations by year
- 2026: 5 · 2025: 3 · 2024: 11 · 2023: 12 · 2022: 13 · 2021: 13 · 2020: 17 · 2019: 11 · 2018: 11 · 2017: 11 · 2016: 16 · 2015: 11 · 2014: 3
- FWCI
- 4.92
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Research Foundation of Korea
- Ministry of Education, Science and Technology (2010-0020274, 2012M3A9C7050093, 2012M3A9C7050184)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Angiogenesis and VEGF in Cancer
- Health Sciences › Medicine › Surgery › Wound Healing and Treatments
- Keywords
- mesenchymal stem cells, TNF-α, endothelial progenitor cells, angiogenesis, EPC homing, interleukin-6, interleukin-8, paracrine signaling, hindlimb ischemia, tissue regeneration, blood perfusion, conditioned medium, immunodepletion
- MeSH terms
- Animals, Cell Movement, Cells, Cultured, Fluorescent Antibody Technique, Hindlimb, Humans, Ischemia, Mice, Nude, Necrosis, Stem Cells, Tumor Necrosis Factor-alpha, Wound Healing, Blotting, Western, Interleukin-6, Interleukin-8, Culture Media, Conditioned, Adipocytes, Neovascularization, Physiologic, Cell Proliferation, Mice, Mesenchymal Stem Cells, Human Umbilical Vein Endothelial Cells
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