Tumor necrosis factor-α-activated mesenchymal stem cells promote endothelial progenitor cell homing and angiogenesis

Kwon, Yang Woo; Heo, Soon Chul; Jeong, Geun Ok; Yoon, Jaesik; Mo, Won Min; Lee, Mi‐Jeong; Jang, Il Ho; Kwon, Sang Mo; Lee, Jung Sub; Kim, Jae Ho

doi:10.1016/j.bbadis.2013.08.002

Cited by 123 publications

(101 citation statements)

References 42 publications

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“…These features, which were significantly different from those of hASCs in 2-dimensional cultures, were likely due to the unique topography cues of DSAF: the DSAF scaffolds had porous nanofibrous structures, which have been reported to affect cellular morphology and function [19, 21–23]. Others have reported that seeded hASCs stabilized HUVECs in vitro and that the paracrine activity of hASCs facilitated tissue angiogenesis in vivo [24]. For this reason, we applied co-cultured hASCs and HUVECs to re-endothelialize DSAF in the present study.…”

Section: Discussionmentioning

confidence: 99%

Decellularized skin/adipose tissue flap matrix for engineering vascularized composite soft tissue flaps

et al. 2016

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Using a perfusion decellularization protocol, we developed a decellularized skin/adipose tissue flap (DSAF) comprising extracellular matrix (ECM) and intact vasculature. Our DSAF had a dominant vascular pedicle, microcirculatory vascularity, and a sensory nerve network and retained three-dimensional (3D) nanofibrous structures well. DSAF, which was composed of collagen and laminin with well-preserved growth factors (e.g., vascular endothelial growth factor, basic fibroblast growth factor), was successfully repopulated with human adipose-derived stem cells (hASCs) and human umbilical vein endothelial cells (HUVECs), which integrated with DSAF and formed 3D aggregates and vessel-like structures in vitro. We used microsurgery techniques to re-anastomose the recellularized DSAF into nude rats. In vivo, the engineered flap construct underwent neovascularization and constructive remodeling, which was characterized by the predominant infiltration of M2 macrophages and significant adipose tissue formation at 3 months postoperatively. Our results indicate that DSAF co-cultured with hASCs and HUVECs is a promising platform for vascularized soft tissue flap engineering. This platform is not limited by the flap size, as the entire construct can be immediately perfused by the recellularized vascular network following simple re-integration into the host using conventional microsurgical techniques.

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Section: Discussionmentioning

confidence: 99%

Decellularized skin/adipose tissue flap matrix for engineering vascularized composite soft tissue flaps

et al. 2016

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“…These data support the concept of fibroblast subset specialization depending upon their cellular origin. Accumulating evidences also demonstrate that BM-MSC promote angiogenesis through the recruitment of endothelial progenitor cells [17], the differentiation into endothelial cells and pericyte-like cells [18], [19], the secretion of soluble angiogenic factors such as Vascular Endothelial Growth Factor(VEGF)-A or basic Fibroblast Growth Factor (bFGF), and the release of exosomes as well [20]–[23].…”

Section: Introductionmentioning

confidence: 99%

Bone Marrow-Derived Mesenchymal Stem Cells Drive Lymphangiogenesis

et al. 2014

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It is now well accepted that multipotent Bone-Marrow Mesenchymal Stem Cells (BM-MSC) contribute to cancer progression through several mechanisms including angiogenesis. However, their involvement during the lymphangiogenic process is poorly described. Using BM-MSC isolated from mice of two different backgrounds, we demonstrate a paracrine lymphangiogenic action of BM-MSC both in vivo and in vitro. Co-injection of BM-MSC and tumor cells in mice increased the in vivo tumor growth and intratumoral lymphatic vessel density. In addition, BM-MSC or their conditioned medium stimulated the recruitment of lymphatic vessels in vivo in an ear sponge assay, and ex vivo in the lymphatic ring assay (LRA). In vitro, MSC conditioned medium also increased the proliferation rate and the migration of both primary lymphatic endothelial cells (LEC) and an immortalized lymphatic endothelial cell line. Mechanistically, these pro-lymphangiogenic effects relied on the secretion of Vascular Endothelial Growth Factor (VEGF)-A by BM-MSC that activates VEGF Receptor (VEGFR)-2 pathway on LEC. Indeed, the trapping of VEGF-A in MSC conditioned medium by soluble VEGF Receptors (sVEGFR)-1, -2 or the inhibition of VEGFR-2 activity by a specific inhibitor (ZM 323881) both decreased LEC proliferation, migration and the phosphorylation of their main downstream target ERK1/2. This study provides direct unprecedented evidence for a paracrine lymphangiogenic action of BM-MSC via the production of VEGF-A which acts on LEC VEGFR-2.

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“…(11) Theoretically, the TNF-α-activated MSCs are able to express various pro-regenerative growth factors, particularly VEGF, platelet-derived growth factor (PDGF), and fibroblast growth factor (FGF), that can activate fibroblasts and impact on collagen synthesis. (9) Previous studies have reported that MSCs activated by the pro-inflammatory cytokine interferon gamma (IFN-γ) are able to increase wound regeneration and tensile strength that is correlated with the amount of collagen. (13) On the other hand, MSCs that are activated in vitro by TNF-α, lipopolysaccharide (LPS) and hypoxia, are able to increase the production of growth factors, particularly VEGF, (14) but the role of TNF-α-activated MSCs on VEGF concentrations and their relationship with collagen are as yet unknown.…”

Section: Introductionmentioning

confidence: 99%

“…(1,8) Several potent pro-inflammatory cytokines, particularly TNF-α, play an important role in MSCs activation. (9,10) Activated MSCs release various molecules, such as prostaglandin E 2 (PGE 2 ) that will bind to their EP4 and EP2 receptors on macrophages, so effecting the polarization of macrophages from the inflammatory into the regenerative type. (11) This is marked by the release of the anti-inflammatory interleukin-10 (IL-10).…”

Section: Introductionmentioning

confidence: 99%

Tumor necrosis factor-α-activated mesenchymal stem cells accelerate wound healing through vascular endothelial growth factor regulation in rats

Nugraha

Putra

2018

Universa Medicina

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Background Wounds are areas of physical or thermal damage of the epithelial layer of skin or mucosa. The wound healing process consists of hemostasis, inflammation, proliferation, and remodeling. Mesenchymal stem cells (MSCs) play a role in wound healing by suppressing potent pro-inflammatory molecules, such as tumor necrosis factor-α (TNF-α), leading to macrophage polarization from the pro-inflammatory type to the pro-regeneration type characterized by increasing vascular endothelial growth factor (VEGF) production. MSCs are able to increase VEGF level in-vivo correlated with collagen synthesis. The objective of this study was to assess the role of TNF-α-activated MSCs on VEGF in rat wounds. Methods An experimental animal study with post-test only control group design was performed involving 24 Wistar rats. The rats were randomized into four groups consisting of one control (K) and three treatment groups (P) (activated MSCs at doses of 3x105, 6x105, and 12x105 cells, respectively). The measurement of VEGF levels was done using ELISA assay while the collagen analysis was performed by light microscopy. One way ANOVA and Post Hoc LSD were used to analyze the data. Results The results showed a significant increase in VEGF levels (p <0.05) on day 3 and then a significant decrease on day 5 along with a significant increase in the amount of collagen on day 7 (p<0.05). Conclusion This study demonstrated that TNF-α-activated MSCs were able to regulate VEGF levels and collagen synthesis in wound healing in rats. The molecular mechanism by which TNF-α-activated MSCs stimulate cutaneous wound healing should be clarified further.

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Tumor necrosis factor-α-activated mesenchymal stem cells promote endothelial progenitor cell homing and angiogenesis

Cited by 123 publications

References 42 publications

Decellularized skin/adipose tissue flap matrix for engineering vascularized composite soft tissue flaps

Decellularized skin/adipose tissue flap matrix for engineering vascularized composite soft tissue flaps

Bone Marrow-Derived Mesenchymal Stem Cells Drive Lymphangiogenesis

Tumor necrosis factor-α-activated mesenchymal stem cells accelerate wound healing through vascular endothelial growth factor regulation in rats

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