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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Mesenchymal stem cell secretome: toward cell-free therapeutic strategies in regenerative medicine
Vizoso, F., Eiro, N., Cid, S., Schneider, J., & Perez-Fernandez, R. (2017) · International Journal of Molecular Sciences · doi:10.3390/ijms18091852 · Cited by 1,363
Mesenchymal Stem Cell Migration and Tissue Repair
Fu, X.-R., Liu, G., Halim, A., Ju, Y., Luo, Q., & Song, G.-B. (2019) · Cells · doi:10.3390/cells8080784 · Cited by 900
The ominous triad of adipose tissue dysfunction: inflammation, fibrosis, and impaired angiogenesis.
Crewe, C., An, Y. A., & Scherer, P. E. (2017) · Journal of Clinical Investigation · doi:10.1172/jci88883 · Cited by 732
“Additionally, several cytokines produced by inflammatory cells have angiogenic effects, including TNF, IL-6, and IL-8 (57, 58).”
Madrigal, M., Rao, K. S. J., & Riordan, N. H. (2014) · Journal of Translational Medicine · doi:10.1186/s12967-014-0260-8 · Cited by 637
“TNF-α pretreatment of MSCs endowed the cells with superior angiogenic activity in vitro, as assessed by expression of VEGF, as well as in vivo in an animal model of critical limb ischemia, as compared to untreated MSCs [81].”
BackgroundBrennan, M. Á., Layrolle, P., & Mooney, D. J. (2020) · Advanced Functional Materials · doi:10.1002/adfm.201909125 · Cited by 399
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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