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.

scholarly journals Exosomes derived from bone marrow mesenchymal stem cells promote angiogenesis via transfer of miR-21-5p after cerebral ischemia in mice

2021 ◽  
Author(s):  
Hui Hu ◽  
xiaowei Hu ◽  
lin Li ◽  
Jingjing Gu ◽  
Yan Fang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cerebral Ischemia ◽  
Western Blot ◽  
Tube Formation ◽  
Neurological Function ◽  
In Vitro Assays ◽  
Marrow Mesenchymal Stem Cells

Abstract Background Mesenchymal stem cells (MSCs) transplantation is a potential clinical therapy for cerebral ischemia. The therapeutic effects of MSCs primarily depends on the paracrine action by releasing exosomes (Exos). Exosomes derived from bone marrow mesenchymal stem cells (BMSC-Exos) could modulate target cell functions by transferring microRNAs (miRs) cargo. In this study, we aimed to investigate whether BMSC-Exos could promote angiogenesis via transfer of miR-21-5p after cerebral ischemia. Methods BMSC-Exos were isolated from conditioned medium of BMSCs by differential ultracentrifugation, and confirmed by transmission electron microscopy, nanoparticle tracking analysis, and western blot analysis. In mice with middle cerebral artery occlusion (MCAO), the neurological function was evaluated by Zea Longa’s method, and the infarct volume and microvessel density were detected by TTC staining and vWF immunofluorescence staining, respectively. The proangiogenic effects of BMSC-Exos were assessed via proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) in vitro assays. The miR-21-5p expression was detected by qRT-PCR. The expression levels of VEGF, VEGFR2, Ang-1, and Tie-2 were determined by western blot. Results BMSC-Exos significantly improved neurological function and reduced infract volume after cerebral ischemia. Moreover, BMSC-Exos significantly upregulated the microvessel density and the expression levels of proangiogenic proteins VEGF, VEGFR2, Ang-1 and Tie-2 in the ischemic boundary region. MiR-21-5p expression was also dramatically increased after cerebral ischemia. In vitro assays revealed that BMSC-Exos enhanced HUVECs functions including proliferation, migration and tube formation, as well as increasing the expression of VEGF and VEGFR2. However, these proangiogenic effects of BMSC-Exos on HUVECs were reversed by miR-21-5p inhibitor. Conclusion Our study indicated that BMSC-Exos could promote angiogenesis and neurological function recovery via transfer of miR-21-5p. Therefore, the application of miR-21-5p-loaded BMSC-Exos might be an attractive treatment strategy of cerebral ischemia.

scholarly journals Exosomes Derived from Human Bone Marrow Mesenchymal Stem Cells Stimulated by Deferoxamine Accelerate Cutaneous Wound Healing by Promoting Angiogenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jianing Ding ◽  
Xin Wang ◽  
Bi Chen ◽  
Jieyuan Zhang ◽  
Jianguang Xu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Wound Healing ◽  
Mesenchymal Stem Cells ◽  
Wound Repair ◽  
Umbilical Vein ◽  
Tube Formation ◽  
Diabetic Rats

The exosomes are derived from mesenchymal stem cells (MSCs) and may be potentially used as an alternative for cell therapy, for treating diabetic wounds, and aid in angiogenesis. This study, aimed to investigate whether exosomes originated from bone marrow-derived MSCs (BMSCs) preconditioned by deferoxamine (DFO-Exos) exhibited superior proangiogenic property in wound repair and to explore the underlying mechanisms involved. Human umbilical vein endothelial cells (HUVECs) were used for assays involving cell proliferation, scratch wound healing, and tube formation. To test the effects in vivo, streptozotocin-induced diabetic rats were established. Two weeks after the procedure, histological analysis was used to measure wound-healing effects, and the neovascularization was evaluated as well. Our findings demonstrated that DFO-Exos activate the PI3K/AKT signaling pathway via miR-126 mediated PTEN downregulation to stimulate angiogenesis in vitro. This contributed to enhanced wound healing and angiogenesis in streptozotocin-induced diabetic rats in vivo. Our results suggest that, in cell-free therapies, exosomes derived from DFO preconditioned stem cells manifest increased proangiogenic ability.

scholarly journals Efficient Differentiation of Bone Marrow Mesenchymal Stem Cells into Endothelial Cells in Vitro

2018 ◽  
Vol 55 (2) ◽  
pp. 257-265 ◽  
Author(s):  
Chengen Wang ◽  
Yuan Li ◽  
Min Yang ◽  
Yinghua Zou ◽  
Huihui Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Marrow Mesenchymal Stem Cells

In vitro-induced differentiation of bone marrow mesenchymal stem cells into melanocytes

2015 ◽  
Vol 39 (7) ◽  
pp. 824-833 ◽  
Author(s):  
Xingyu Mei ◽  
Yue Sun ◽  
Zhouwei Wu ◽  
Weihua Pan ◽  
Jianyu Zhu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Induced Differentiation ◽  
Marrow Mesenchymal Stem Cells

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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