scholarly journals Exosomes from adipose tissue-derived mesenchymal stem cells ameliorate histone-induced acute lung injury by activating the PI3K/Akt pathway in endothelial cells

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Yukie Mizuta ◽  
Tomohiko Akahoshi ◽  
Jie Guo ◽  
Shuo Zhang ◽  
Sayoko Narahara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Lung Damage ◽  
Akt Pathway ◽  
Pulmonary Vascular Permeability ◽  
Paracrine Effect ◽  
Akt Phosphorylation

Abstract Background Mesenchymal stem cells (MSCs), including adipose-derived mesenchymal stem cells (ADSCs), have been shown to attenuate organ damage in acute respiratory distress syndrome (ARDS) and sepsis; however, the underlying mechanisms are not fully understood. In this study, we aimed to explore the potential roles and molecular mechanisms of action of ADSCs in histone-induced endothelial damage. Methods Male C57BL/6 N mice were intravenously injected with ADSCs, followed by histones or a vehicle. The mice in each group were assessed for survival, pulmonary vascular permeability, and histological changes. A co-culture model with primary human umbilical vein endothelial cells (HUVECs) exposed to histones was used to clarify the paracrine effect of ADSCs. Overexpression and inhibition of miR-126 ADSCs were also examined as causative factors for endothelial protection. Results The administration of ADSCs markedly improved survival, inhibited histone-mediated lung hemorrhage and edema, and attenuated vascular hyper-permeability in mice. ADSCs were engrafted in the injured lung and attenuated histone-induced endothelial cell apoptosis. ADSCs showed endothelial protection (via a paracrine effect) and Akt phosphorylation in the histone-exposed HUVECs. Notably, increased Akt phosphorylation by ADSCs was mostly mediated by exosomes in histone-induced cytotoxicity and lung damage. Moreover, the expression of miR-126 was increased in exosomes from histone-exposed ADSCs. Remarkably, the inhibition of miR-126 in ADSCs failed to increase Akt phosphorylation in histone-exposed HUVECs. Conclusion ADSC-derived exosomes may exert protective effects on endothelial cells via activation of the PI3K/Akt pathway.

scholarly journals Exosomes from Adipose Tissue-Derived Mesenchymal Stem Cells Ameliorate Histone-Induced Acute Lung Injury by Activating the PI3K/Akt Pathway in Endothelial Cells.

2020 ◽  
Author(s):  
Yukie Mizuta ◽  
Tomohiko Akahoshi ◽  
Jie Guo ◽  
Shuo Zhang ◽  
Sayoko Narahara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Lung Damage ◽  
Akt Pathway ◽  
Pulmonary Vascular Permeability ◽  
Paracrine Effect ◽  
Akt Phosphorylation

Abstract BackgroundMesenchymal stem cells (MSCs), including adipose-derived mesenchymal stem cells (ADSCs), have been shown to attenuate organ damage in acute respiratory distress syndrome (ARDS) and sepsis; however, the underlying mechanisms have not been fully understood. In this study, we aimed to explore the potential roles and molecular mechanisms of action of ADSCs in histone-induced endothelial damage. MethodsMale C57BL/6N mice were intravenously injected with ADSCs, followed by histones or a vehicle. The mice in each group were assessed for survival, pulmonary vascular permeability, and histological changes. A co-culture model with primary human umbilical vein endothelial cells (HUVECs) exposed to histones was used to clarify the paracrine effect of ADSCs. Overexpression and inhibition of miR-126 ADSCs were also examined as causative factors for endothelial protection.ResultsThe administration of ADSCs markedly improved survival, inhibited histone-mediated lung hemorrhage and edema, and attenuated vascular hyper-permeability in mice. ADSCs were engrafted in the injured lung and attenuated histone-induced endothelial cell apoptosis. ADSCs showed endothelial protection (via a paracrine effect) and Akt phosphorylation in the histone-exposed HUVECs. Notably, increased Akt phosphorylation by ADSCs was mostly mediated by exosomes in histone-induced cytotoxicity and lung damage. Moreover, inhibition of miR-126, which is known to be present in exosomes, in ADSCs did not increase Akt phosphorylation in histone-exposed HUVECs. ConclusionADSC-derived exosomes may exert protective effects on endothelial cells via activation of the PI3K/Akt pathway.

scholarly journals Exosomes from adipose tissue-derived mesenchymal stem cells ameliorate histone-induced acute lung injury by activating the PI3K/Akt pathway in endothelial cells.

2020 ◽  
Author(s):  
Yukie Mizuta ◽  
Tomohiko Akahoshi ◽  
Jie Guo ◽  
Shuo Zhang ◽  
Sayoko Narahara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Molecular Mechanisms ◽  
Umbilical Vein ◽  
Lung Damage ◽  
Akt Pathway ◽  
Pulmonary Vascular Permeability ◽  
Paracrine Effect ◽  
Akt Phosphorylation

Abstract BackgroundMesenchymal stem cells (MSCs), including adipose-derived mesenchymal stem cells (ADSCs), have been shown to attenuate organ damage in acute respiratory distress syndrome (ARDS) and sepsis; however, the underlying mechanisms are not fully understood. In this study, we aimed to explore the potential roles and molecular mechanisms of action of ADSCs in histone-induced endothelial damage. MethodsMale C57BL/6N mice were intravenously injected with ADSCs, followed by histones or a vehicle. The mice in each group were assessed for survival, pulmonary vascular permeability, and histological changes. A co-culture model with primary human umbilical vein endothelial cells (HUVECs) exposed to histones was used to clarify the paracrine effect of ADSCs. Overexpression and inhibition of miR-126 ADSCs were also examined as causative factors for endothelial protection.ResultsThe administration of ADSCs markedly improved survival, inhibited histone-mediated lung hemorrhage and edema, and attenuated vascular hyper-permeability in mice. ADSCs were engrafted in the injured lung and attenuated histone-induced endothelial cell apoptosis. ADSCs showed endothelial protection (via a paracrine effect) and Akt phosphorylation in the histone-exposed HUVECs. Notably, increased Akt phosphorylation by ADSCs was mostly mediated by exosomes in histone-induced cytotoxicity and lung damage. Moreover, the expression of miR-126 was increased in exosomes from histone-exposed ADSCs. Remarkably, the inhibition of miR-126 in ADSCs failed to increase Akt phosphorylation in histone-exposed HUVECs. ConclusionADSC-derived exosomes may exert protective effects on endothelial cells via activation of the PI3K/Akt pathway.

scholarly journals Paracrine Interleukin-8 affects mesenchymal stem cells through the Akt pathway and enhances human umbilical vein endothelial cell proliferation and migration

2021 ◽  
Author(s):  
Lulu wang ◽  
Yongtao Li ◽  
Xiaodong Zhang ◽  
Na Liu ◽  
Shiyang Shen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
High Glucose ◽  
Umbilical Vein ◽  
Interleukin 8 ◽  
Akt Pathway ◽  
Human Umbilical Vein ◽  
And Migration ◽  
Proliferation And Migration

Interleukin-8 (IL-8) promotes cell homing and angiogenesis, but its effects on activating human bone marrow mesenchymal stem cells (BMSCs) and promoting angiogenesis are unclear. We used bioinformatics to predict these processes. In vitro, BMSCs were stimulated in a high-glucose (HG) environment with 50 μg/mL or 100 μg/mL IL-8 were used as the IL-8 group. 5μmol/L Triciribine was added to the two IL-8 groups as the Akt inhibitor group. Cultured human umbilical vein endothelial cells (HUVECs) were cultured in BMSCs conditioned medium (CM). Observe the changes in proliferation, apoptosis, migration ability and levels of VEGF and IL-6 in HUVEC each group. 70 processes and 26 pathways were involved in vascular development, through which IL-8 affected BMSCs. Compared with the high-glucose control group, HUVEC proliferation A value, Gap closure rate, and Transwell cell migration rate in the IL-8 50 and IL-8 100 CM groups were significantly increased (P<0.01, n=30). However, HUVEC apoptosis was significantly decreased (P<0.01, n=30). Akt and phospho-Akt protein contents in lysates of BMSCs treated with IL-8, as well as VEGF and IL-6 protein contents in the supernatant of BMSCs treated with IL-8, were all highly expressed (P<0.01, n=15). These analyses confirmed that IL-8 promoted the expression of 41 core proteins in BMSCs through the PI3K Akt pathway, which could promote the proliferation and migration of vascular endothelial cells. Therefore, in a high-glucose environment, IL-8 activated the Akt signaling pathway, promoted paracrine mechanisms of BMSCs, and improved the proliferation and migration of HUVECs.

scholarly journals Effect of Chemically Induced Hypoxia on Osteogenic and Angiogenic Differentiation of Bone Marrow Mesenchymal Stem Cells and Human Umbilical Vein Endothelial Cells in Direct Coculture

Cells ◽  
2020 ◽  
Vol 9 (3) ◽  
pp. 757
Author(s):  
Van Thi Nguyen ◽  
Barbara Canciani ◽  
Federica Cirillo ◽  
Luigi Anastasia ◽  
Giuseppe M. Peretti ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Blood Vessels ◽  
Umbilical Vein ◽  
Human Umbilical Vein ◽  
Chemically Induced ◽  
Umbilical Vein Endothelial Cells

Bone is an active tissue where bone mineralization and resorption occur simultaneously. In the case of fracture, there are numerous factors required to facilitate bone healing including precursor cells and blood vessels. To evaluate the interaction between bone marrow-derived mesenchymal stem cells (BMSC)—the precursor cells able to differentiate into bone-forming cells and human umbilical vein endothelial cells (HUVEC)—a cell source widely used for the study of blood vessels. We performed direct coculture of BMSC and HUVEC in normoxia and chemically induced hypoxia using Cobalt(II) chloride and Dimethyloxaloylglycine and in the condition where oxygen level was maintained at 1% as well. Cell proliferation was analyzed by crystal violet staining. Osteogenesis was examined by Alizarin Red and Collagen type I staining. Expression of angiogenic factor-vascular endothelial growth factor (VEGF) and endothelial marker-von Willebrand factor (VWF) were demonstrated by immunohistochemistry and enzyme-linked immunosorbent assay. The quantitative polymerase chain reaction was also used to evaluate gene expression. The results showed that coculture in normoxia could retain both osteogenic differentiation and endothelial markers while hypoxic condition limits cell proliferation and osteogenesis but favors the angiogenic function even after 1 of day treatment.

Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells

Blood ◽  
2006 ◽  
Vol 108 (12) ◽  
pp. 3938-3944 ◽  
Author(s):  
Brigitte Rüster ◽  
Stephan Göttig ◽  
Ralf J. Ludwig ◽  
Roxana Bistrian ◽  
Stefanie Müller ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Mononuclear Cells ◽  
Umbilical Vein ◽  
Shear Stresses ◽  
Human Mscs ◽  
Dependent Manner ◽  
Peripheral Blood Mononuclear

AbstractTo explore the initial steps by which transplanted mesenchymal stem cells (MSCs) interact with the vessel wall in the course of extravasation, we studied binding of human MSCs to endothelial cells (ECs). In a parallel plate flow chamber, MSCs bound to human umbilical vein ECs (HUVECs) similar to peripheral-blood mononuclear cells (PBMCs) or CD34+ hematopoietic progenitors at shear stresses of up to 2 dynes/cm2. This involved rapid extension of podia, rolling, and subsequent firm adhesion that was increased when ECs were prestimulated with TNF-α. MSC binding was suppressed when ECs were pretreated with function-blocking anti–P-selectin antibody, and rolling of MSCs was induced on immobilized P-selectin, indicating that P-selectin was involved in this process. Preincubation of HUVECs with anti–VCAM-1 or of MSCs with anti–VLA-4 antibodies suppressed binding of MSCs to HUVECs but did not enhance inhibition by anti–P-selectin, indicating that both P-selectin and VCAM-1 are equally required for this process. Intravital microscopy demonstrated the capacity of MSCs to roll and adhere to postcapillary venules in vivo in a mouse model in a P-selectin–dependent manner. Thus, MSCs interact in a coordinated fashion with ECs under shear flow, engaging P-selectin and VCAM-1/VLA-4.

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