Adipose-Derived Stem Cells Promote Proliferation, Migration, and Tube Formation of Lymphatic Endothelial Cells In Vitro by Secreting Lymphangiogenic Factors

2015 ◽  
Vol 74 (6) ◽  
pp. 728-736 ◽  
Author(s):  
Kohsuke Takeda ◽  
Yoshihiro Sowa ◽  
Kenichi Nishino ◽  
Kyoko Itoh ◽  
Shinji Fushiki
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Tube Formation ◽  
Adipose Derived Stem Cells ◽  
Lymphatic Endothelial Cells

scholarly journals Exosomes derived from adipose-derived stem cells overexpressing glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Xing Zhang ◽  
Yihong Jiang ◽  
Qun Huang ◽  
Zhaoyu Wu ◽  
Hongji Pu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Limb Ischemia ◽  
Tube Formation ◽  
Adipose Derived Stem Cells ◽  
Diabetic Mice ◽  
Type 2 Diabetic

Abstract Background Diabetic limb ischemia is a clinical syndrome and refractory to therapy. Our previous study demonstrated that adipose-derived stem cells (ADSCs) overexpressing glyoxalase-1 (GLO-1) promoted the regeneration of ischemic lower limbs in diabetic mice, but low survival rate, difficulty in differentiation, and tumorigenicity of the transplanted cells restricted its application. Recent studies have found that exosomes secreted by the ADSCs have the advantages of containing parental beneficial factors and exhibiting non-immunogenic, non-tumorigenic, and strong stable characteristics. Methods ADSCs overexpressing GLO-1 (G-ADSCs) were established using lentivirus transfection, and exosomes secreted from ADSCs (G-ADSC-Exos) were isolated and characterized to coculture with human umbilical vein endothelial cells (HUVECs). Proliferation, apoptosis, migration, and tube formation of the HUVECs were detected under high-glucose conditions. The G-ADSC-Exos were injected into ischemic hindlimb muscles of type 2 diabetes mellitus (T2DM) mice, and the laser Doppler perfusion index, Masson’s staining, immunofluorescence, and immunohistochemistry assays were adopted to assess the treatment efficiency. Moreover, the underlying regulatory mechanisms of the G-ADSC-Exos on the proliferation, migration, angiogenesis, and apoptosis of the HUVECs were explored. Results The G-ADSC-Exos enhanced the proliferation, migration, tube formation, and anti-apoptosis of the HUVECs in vitro under high-glucose conditions. After in vivo transplantation, the G-ADSC-Exo group showed significantly higher laser Doppler perfusion index, better muscle structural integrity, and higher microvessel’s density than the ADSC-Exo and control groups by Masson’s staining and immunofluorescence assays. The underlying mechanisms by which the G-ADSC-Exos protected endothelial cells both in vitro and in vivo might be via the activation of eNOS/AKT/ERK/P-38 signaling pathways, inhibition of AP-1/ROS/NLRP3/ASC/Caspase-1/IL-1β, as well as the increased secretion of VEGF, IGF-1, and FGF. Conclusion Exosomes derived from adipose-derived stem cells overexpressing GLO-1 protected the endothelial cells and promoted the angiogenesis in type 2 diabetic mice with limb ischemia, which will be a promising clinical treatment in diabetic lower limb ischemia.

scholarly journals Exosomes derived from adipose-derived stem cells overexpressing Glyoxalase-1 protect endothelial cells and enhance angiogenesis in type 2 diabetic mice with limb ischemia

2021 ◽  
Author(s):  
Xing Zhang ◽  
Yihong Jiang ◽  
Qun Huang ◽  
Zhaoyu Wu ◽  
Hongji Pu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Limb Ischemia ◽  
Tube Formation ◽  
Adipose Derived Stem Cells ◽  
Diabetic Mice ◽  
Type 2 Diabetic

Abstract Background: Diabetic limb ischemia is a clinical syndrome and refractory to therapy. Our previous study demonstrated that adipose-derived stem cells (ADSCs) overexpressing glyoxalase-1 (GLO-1) promoted the regeneration of ischemic lower limbs in diabetic mice, but low survival rate, difficulty in differentiation, and tumorigenicity of the transplanted cells restricted its application. Recent studies have found that exosomes secreted by the ADSCs have the advantages of containing parental beneficial factors and exhibiting non-immunogenic, non-tumorigenic, and strong stable characteristics.Methods: ADSCs overexpressing GLO-1 (G-ADSCs) were established using lentivirus transfection, and exosomes secreted ADSCs (G-ADSC-Exos) were isolated and characterized to co-culture with human umbilical vein endothelial cells (HUVECs). Proliferation, apoptosis, migration, and tube formation of the HUVECs were detected under high glucose conditions. The G-ADSC-Exos were injected into ischemic hindlimb muscles of type 2 diabetes mellitus (T2DM) mice, and the laser Doppler perfusion index, Masson’s staining, immunofluorescence and immunohistochemistry assays were adopted to assess the treatment efficiency. Moreover, the underlying regulatory mechanisms of the G-ADSC-Exos on the proliferation, migration, angiogenesis, and apoptosis of the HUVECs were explored.Results: The G-ADSC-Exos enhanced the proliferation, migration, tube formation, and anti-apoptosis of the HUVECs in vitro under high glucose conditions. After in vivo transplantation, the G-ADSC-Exo group showed significantly higher laser Doppler perfusion index, better muscle structural integrity, and higher microvessel’s density than the ADSC-Exo and control groups by Masson’s staining, and immunofluorescence assays. The underlying mechanisms by which the G-ADSC-Exos protected endothelial cells both in vitro and in vivo might be via the activation of eNOS/AKT/ERK/P-38 signaling pathways, inhibition of AP-1/ROS/NLRP3/ASC/Caspase-1/IL-1β, as well as the increased secretion of VEGF, IGF-1, and FGF.Conclusion: Exosomes derived from adipose-derived stem cells overexpressing GLO-1 protected the endothelial cells and promoted the angiogenesis in type 2 diabetic mice with limb ischemia, which will be a promising clinical treatment in diabetic lower limb ischemia.

scholarly journals Paracrine effect of human adipose-derived stem cells on lymphatic endothelial cells

2020 ◽  
Vol 15 (9) ◽  
pp. 2085-2098
Author(s):  
Cristiana Marcozzi ◽  
Annalisa Frattini ◽  
Marina Borgese ◽  
Federica Rossi ◽  
Ludovica Barone ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Conditioned Medium ◽  
Lymphatic Vessels ◽  
Lymphatic Endothelial Cell ◽  
Adipose Derived Stem Cells ◽  
Lymphatic Endothelial Cells ◽  
Paracrine Effect ◽  
Secondary Lymphedema

Aim: The proposal of this study was to evaluate, in vitro, the potential paracrine effect of human adipose-derived stem cells (hASCs) to promote lymphangiogenesis in lymphatic endothelial cells isolated from rat diaphragmatic lymphatic vessels. Materials & methods: ELISA on VEGFA, VEGFC and IL6 in hASC-conditioned medium; LYVE1 immunostaining; and gene expression of PROX1, VEGFR3, VEGFC, VEGFA and IL6 were the methods used. Results: In 2D culture, hASC-conditioned medium was able to promote lymphatic endothelial cell survival, maintenance of endothelial cobblestone morphology and induction to form a vessel-like structure. Conclusion: The authors' results represent in vitro evidence of the paracrine effect of hASCs on lymphatic endothelial cells, suggesting the possible role of hASC-conditioned medium in developing new therapeutic approaches for lymphatic system-related dysfunction such as secondary lymphedema.

scholarly journals Atherogenic Cytokines Regulate VEGF-A-Induced Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells into Endothelial Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Izuagie Attairu Ikhapoh ◽  
Christopher J. Pelham ◽  
Devendra K. Agrawal
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Tube Formation ◽  
Ang Ii ◽  
Induced Differentiation ◽  
Endothelial Tube Formation ◽  
Marker Expression

Coronary artery stenting or angioplasty procedures frequently result in long-term endothelial dysfunction or loss and complications including arterial thrombosis and myocardial infarction. Stem cell-based therapies have been proposed to support endothelial regeneration. Mesenchymal stem cells (MSCs) differentiate into endothelial cells (ECs) in the presence of VEGF-Ain vitro. Application of VEGF-A and MSC-derived ECs at the interventional site is a complex clinical challenge. In this study, we examined the effect of atherogenic cytokines (IL-6, TNFα, and Ang II) on EC differentiation and function. MSCs (CD44+, CD73+, CD90+, CD14−, and CD45−) were isolated from the bone marrow of Yucatan microswine. Naïve MSCs cultured in differentiation media containing VEGF-A (50 ng/mL) demonstrated increased expression of EC-specific markers (vWF, PECAM-1, and VE-cadherin), VEGFR-2 and Sox18, and enhanced endothelial tube formation. IL-6 or TNFαcaused a dose-dependent attenuation of EC marker expression in VEGF-A-stimulated MSCs. In contrast, Ang II enhanced EC marker expression in VEGF-A-stimulated MSCs. Addition of Ang II to VEGF-A and IL-6 or TNFαwas sufficient to rescue the EC phenotype. Thus, Ang II promotes but IL-6 and TNFαinhibit VEGF-A-induced differentiation of MSCs into ECs. These findings have important clinical implications for therapies intended to increase cardiac vascularity and reendothelialize coronary arteries following intervention.

IL‐7 enhances the differentiation of adipose‐derived stem cells toward lymphatic endothelial cells through AKT signaling

2019 ◽  
Vol 43 (4) ◽  
pp. 394-401 ◽  
Author(s):  
Yiyu Sun ◽  
Bolun Lu ◽  
Jingcheng Deng ◽  
Zhaohua Jiang ◽  
Weigang Cao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Akt Signaling ◽  
Adipose Derived Stem Cells ◽  
Lymphatic Endothelial Cells

Adipose-derived stem cells induce vascular tube formation of outgrowth endothelial cells in a fibrin matrix

2012 ◽  
Vol 9 (2) ◽  
pp. 127-136 ◽  
Author(s):  
Wolfgang Holnthoner ◽  
Karin Hohenegger ◽  
Anna-Maria Husa ◽  
Severin Muehleder ◽  
Alexandra Meinl ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Tube Formation ◽  
Adipose Derived Stem Cells ◽  
Fibrin Matrix

scholarly journals Exposure to blue light stimulates the proangiogenic capability of exosomes derived from human umbilical cord mesenchymal stem cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Kun Yang ◽  
Dong Li ◽  
Meitian Wang ◽  
Zhiliang Xu ◽  
Xiao Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Blue Light ◽  
Umbilical Cord ◽  
Tube Formation ◽  
Human Umbilical Cord ◽  
Light Illumination

Abstract Background The therapeutic potential of mesenchymal stem cells (MSCs) may be attributed partly to the secreted paracrine factors, which comprise exosomes. Exosomes are small, saucer-shaped vesicles containing miRNAs, mRNAs, and proteins. Exosomes derived from human umbilical cord mesenchymal stem cells (hUC-MSCs) have been reported to promote angiogenesis. However, the efficacy of exosome-based therapies is still limited both in vitro and in vivo. The present study aimed to develop a new optical manipulation approach to stimulate the proangiogenic potential of exosomes and characterize its mechanism underlying tissue regeneration. Methods We used blue (455 nm) and red (638 nm) monochromatic light exposure to investigate the processing of stimuli. Exosomes were prepared by QIAGEN exoEasy Maxi kit and confirmed to be present by transmission electron microscopy and immunoblotting analyses. The proangiogenic activity of blue light-treated human umbilical vein endothelial cells (HUVECs), when co-cultured with hUC-MSCs, was assessed by EdU (5-ethynyl-2′-deoxyuridine) incorporation, wound closure, and endothelial tube formation assays. The in vivo angiogenic activity of blue light-treated MSC-derived exosomes (MSC-Exs) was evaluated using both murine matrigel plug and skin wound models. Results We found that 455-nm blue light is effective for promoting proliferation, migration, and tube formation of HUVECs co-cultured with MSCs. Furthermore, MSC-Exs stimulated in vivo angiogenesis and their proangiogenic potential were enhanced significantly upon blue light illumination. Finally, activation of the endothelial cells in response to stimulation by blue light-treated exosomes was demonstrated by upregulation of two miRNAs, miR-135b-5p, and miR-499a-3p. Conclusions Blue (455 nm) light illumination improved the therapeutic effects of hUC-MSC exosomes by enhancing their proangiogenic ability in vitro and in vivo with the upregulation of the following two miRNAs: miR-135b-5p and miR-499a-3p. Graphical abstract

scholarly journals Tropoelastin Promotes the Formation of Dense, Interconnected Endothelial Networks

Biomolecules ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1318
Author(s):  
Aleen Al Halawani ◽  
Lea Abdulkhalek ◽  
Suzanne M. Mithieux ◽  
Anthony S. Weiss
Keyword(s):  
Stem Cells ◽  
Wound Healing ◽  
Endothelial Cells ◽  
Wound Repair ◽  
Cultured Cells ◽  
Tube Formation ◽  
Endothelial Tube Formation ◽  
Angiogenic Effect

Tropoelastin, the soluble precursor of elastin, has been used for regenerative and wound healing purposes and noted for its ability to accelerate wound repair by enhancing vascularization at the site of implantation. However, it is not clear whether these effects are directly due to the interaction of tropoelastin with endothelial cells or communicated to endothelial cells following interactions between tropoelastin and neighboring cells, such as mesenchymal stem cells (MSCs). We adapted an endothelial tube formation assay to model in vivo vascularization with the goal of exploring the stimulatory mechanism of tropoelastin. In the presence of tropoelastin, endothelial cells formed less tubes, with reduced spreading into capillary-like networks. In contrast, conditioned media from MSCs that had been cultured on tropoelastin enhanced the formation of more dense, complex, and interconnected endothelial tube networks. This pro-angiogenic effect of tropoelastin is mediated indirectly through the action of tropoelastin on co-cultured cells. We conclude that tropoelastin inhibits endothelial tube formation, and that this effect is reversed by pro-angiogenic crosstalk from tropoelastin-treated MSCs. Furthermore, we find that the known in vivo pro-angiogenic effects of tropoelastin can be modeled in vitro, highlighting the value of tropoelastin as an indirect mediator of angiogenesis.

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