scholarly journals Mechanically Stretched Mesenchymal Stem Cells Can Reduce the Effects of LPS-Induced Injury on the Pulmonary Microvascular Endothelium Barrier

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Jin-ze Li ◽  
Shan-shan Meng ◽  
Xiu-Ping Xu ◽  
Yong-bo Huang ◽  
Pu Mao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Mechanical Stretch ◽  
Inflammatory Factors ◽  
Microvascular Endothelial Cell ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Microvascular Endothelium

Mesenchymal stem cells (MSCs) may improve the treatment of acute respiratory distress syndrome (ARDS). However, few studies have investigated the effects of mechanically stretched -MSCs (MS-MSCs) in in vitro models of ARDS. The aim of this study was to evaluate the potential therapeutic effects of MS-MSCs on pulmonary microvascular endothelium barrier injuries induced by LPS. We introduced a cocultured model of pulmonary microvascular endothelial cell (EC) and MSC medium obtained from MSCs with or without mechanical stretch. We found that Wright-Giemsa staining revealed that MSC morphology changed significantly and cell plasma shrank separately after mechanical stretch. Cell proliferation of the MS-MSC groups was much lower than the untreated MSC group; expression of cell surface markers did not change significantly. Compared to the medium from untreated MSCs, inflammatory factors elevated statistically in the medium from MS-MSCs. Moreover, the paracellular permeability of endothelial cells treated with LPS was restored with a medium from MS-MSCs, while LPS-induced EC apoptosis decreased. In addition, protective effects on the remodeling of intercellular junctions were observed when compared to LPS-treated endothelial cells. These data demonstrated that the MS-MSC groups had potential therapeutic effects on the LPS-treated ECs; these results might be useful in the treatment of ARDS.

scholarly journals Propofol attenuates lung ischemia/reperfusion injury though the involvement of the MALAT1/microRNA-144/GSK3β axis

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jian-Ping Zhang ◽  
Wei-Jing Zhang ◽  
Miao Yang ◽  
Hua Fang
Keyword(s):  
Cell Apoptosis ◽  
Ischemia Reperfusion Injury ◽  
Glycogen Synthase ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Loss Of Function

Abstract Background Propofol, an intravenous anesthetic, was proven to protect against lung ischemia/reperfusion (I/R) injury. However, the detailed mechanism of Propofol in lung I/R injury is still elusive. This study was designed to explore the therapeutic effects of Propofol, both in vivo and in vitro, on lung I/R injury and the underlying mechanisms related to metastasis-associated lung adenocarcinoma transcript 1 (MALAT1)/microRNA-144 (miR-144)/glycogen synthase kinase-3β (GSK3β). Methods C57BL/6 mice were used to establish a lung I/R injury model while pulmonary microvascular endothelial cells (PMVECs) were constructed as hypoxia/reperfusion (H/R) cellular model, both of which were performed with Propofol treatment. Gain- or loss-of-function approaches were subsequently employed, followed by observation of cell apoptosis in lung tissues and evaluation of proliferative and apoptotic capabilities in H/R cells. Meanwhile, the inflammatory factors, autophagosomes, and autophagy-related proteins were measured. Results Our experimental data revealed that Propofol treatment could decrease the elevated expression of MALAT1 following I/R injury or H/R induction, indicating its protection against lung I/R injury. Additionally, overexpressing MALAT1 or GSK3β promoted the activation of autophagosomes, proinflammatory factor release, and cell apoptosis, suggesting that overexpressing MALAT1 or GSK3β may reverse the protective effects of Propofol against lung I/R injury. MALAT1 was identified to negatively regulate miR-144 to upregulate the GSK3β expression. Conclusion Overall, our study demonstrated that Propofol played a protective role in lung I/R injury by suppressing autophagy and decreasing release of inflammatory factors, with the possible involvement of the MALAT1/miR-144/GSK3β axis.

scholarly journals Stem Cell-Engineered Nanovesicles Exert Proangiogenic and Neuroprotective Effects

Materials ◽  
2021 ◽  
Vol 14 (5) ◽  
pp. 1078
Author(s):  
Han Young Kim ◽  
Suk Ho Bhang
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Tissue Regeneration ◽  
Therapeutic Agent ◽  
Therapeutic Effects ◽  
Hydrodynamic Size ◽  
Regeneration Strategy ◽  
Neuroprotective Effects ◽  
The Poor

As a tissue regeneration strategy, the utilization of mesenchymal stem cells (MSCs) has drawn considerable attention. Comprehensive research using MSCs has led to significant preclinical or clinical outcomes; however, improving the survival rate, engraftment efficacy, and immunogenicity of implanted MSCs remains challenging. Although MSC-derived exosomes were recently introduced and reported to have great potential to replace conventional MSC-based therapeutics, the poor production yield and heterogeneity of exosomes are critical hurdles for their further applications. Herein, we report the fabrication of exosome-mimetic MSC-engineered nanovesicles (MSC-NVs) by subjecting cells to serial extrusion through filters. The fabricated MSC-NVs exhibit a hydrodynamic size of ~120 nm, which is considerably smaller than the size of MSCs (~30 μm). MSC-NVs contain both MSC markers and exosome markers. Importantly, various therapeutic growth factors originating from parent MSCs are encapsulated in the MSC-NVs. The MSC-NVs exerted various therapeutic effects comparable to those of MSCs. They also significantly induced the angiogenesis of endothelial cells and showed neuroprotective effects in damaged neuronal cells. The results collectively demonstrate that the fabricated MSC-NVs can serve as a nanosized therapeutic agent for tissue regeneration.

Abstract 558: Microchanneled Polysaccharide Hydrogel Laden With Endothelial Cells and Mesenchymal Stem Cells With VEGF Facilitate Formation of Vascular Structures and Are Effective for Repairing Tissue Ischemia

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Sangho Lee ◽  
Min Kyung Lee ◽  
Hyunjoon Kong ◽  
Young-sup Yoon
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Cell Survival ◽  
Vascular Structure ◽  
Hindlimb Ischemia ◽  
Alginate Hydrogel ◽  
Vessel Formation

Various hydrogels are used to create vascular structure in vitro or to improve cell engraftment to overcome low cell survival in vivo, a main hurdle for bare cell therapy Recently we developed a modified alginate hydrogel within which microchannels are aligned to guide the direction and spatial organization of loaded cells. We investigated whether these cell constructs in which HUVECs and human mesenchymal stem cells (hMSCs) are co-loaded in this novel microchanneled hydrogel facilitate formation of vessels in vitro and in vivo, and enhance recovery of hindlimb ischemia. We crafted a modified alginate hydrogel which has microchannels, incorporates a cell adhesion peptide RGD, and was encapsulated with VEGF. We then compared vascular structure formation between the HUVEC only (2 x 105 cells) group and the HUVEC plus hMSC group. In the HUVEC+hMSC group, we mixed HUVECs and hMSCs at the ratio of 3:1. For cell tracking, we labeled HUVECs with DiO, a green fluorescence dye. After loading cells into the microchannels of the hydrogel, these constructs were cultured for seven days and were examined by confocal microscopy. In the HUVEC only group, HUVECs stands as round shaped cells without forming tubular structures within the hydrogel. However, in the HUVEC+hMSC group, HUVECs were stretched out and connected with each other, and formed vessel-like structure following pre-designed microchannels. These results suggested that hMSCs play a critical role for vessel formation by HUVECs. We next determined their in vivo effects using a mouse hindlimb ischemia model. We found that engineered HUVEC+hMSC group showed significantly higher perfusion over 4 weeks compared to the engineered HUVEC only group or bare cell (HUVEC) group. Confocal microscopic analysis of harvested tissues showed more robust vessel formation within and outside of the cell constructs and longer term cell survival in HUVEC+hMSC group compared to the other groups. In conclusion, this novel microchanneled alginate hydrogel facilitates aligned vessel formation of endothelial cells when combined with MSCs. This vessel-embedded hydrogel constructs consisting of HUVECs and MSCs contribute to perfusable vessel formation, prolong cell survival in vivo, and are effective for recovering limb ischemia.

scholarly journals Positively Correlated CD47 Activation and Autophagy in Umbilical Cord Blood-Derived Mesenchymal Stem Cells during Senescence

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Gee-Hye Kim ◽  
Yun Kyung Bae ◽  
Ji Hye Kwon ◽  
Miyeon Kim ◽  
Soo Jin Choi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Stem Cell ◽  
Cell Growth ◽  
Cell Therapy ◽  
Critical Role ◽  
Therapeutic Effects ◽  
Stem Cell Maintenance ◽  
Selection Of

Autophagy plays a critical role in stem cell maintenance and is related to cell growth and cellular senescence. It is important to find a quality-control marker for predicting senescent cells. This study verified that CD47 could be a candidate to select efficient mesenchymal stem cells (MSCs) to enhance the therapeutic effects of stem cell therapy by analyzing the antibody surface array. CD47 expression was significantly decreased during the expansion of MSCs in vitro ( p < 0.01 ), with decreased CD47 expression correlated with accelerated senescence phenotype, which affected cell growth. UCB-MSCs transfected with CD47 siRNA significantly triggered the downregulation of pRB and upregulation of pp38, which are senescence-related markers. Additionally, autophagy-related markers, ATG5, ATG12, Beclin1, and LC3B, revealed significant downregulation with CD47 siRNA transfection. Furthermore, autophagy flux following treatment with an autophagy inducer, rapamycin, has shown that CD47 is a key player in autophagy and senescence to maintain and regulate the growth of MSCs, suggesting that CD47 may be a critical key marker for the selection of effective stem cells in cell therapy.

scholarly journals Protective effects of ginsenoside Rg1 on intestinal ischemia/reperfusion injury-induced oxidative stress and apoptosis via activation of the Wnt/β-catenin pathway

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Guo Zu ◽  
Jing Guo ◽  
Ningwei Che ◽  
Tingting Zhou ◽  
Xiangwen Zhang
Keyword(s):  
Signaling Pathway ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inflammatory Factors ◽  
Therapeutic Effects ◽  
Protective Effects ◽  
Ginsenoside Rg1 ◽  
Intestinal Ischemia Reperfusion

Abstract Ginsenoside Rg1 (Rg1) is one of the major bioactive ingredients in Panax ginseng, and it attenuates inflammation and apoptosis. The aims of our study were to explore the potential of Rg1 for the treatment of intestinal I/R injury and to determine whether the protective effects of Rg1 were exerted through the Wnt/β-catenin signaling pathway. In this study, Rg1 treatment ameliorated inflammatory factors, ROS and apoptosis that were induced by intestinal I/R injury. Cell viability was increased and cell apoptosis was decreased with Rg1 pretreatment following hypoxia/reoxygenation (H/R) in the in vitro study. Rg1 activated the Wnt/β-catenin signaling pathway in both the in vivo and in vitro models, and in the in vitro study, the activation was blocked by DKK1. Our study provides evidence that pretreatment with Rg1 significantly reduces ROS and apoptosis induced by intestinal I/R injury via activation of the Wnt/β-catenin pathway. Taken together, our results suggest that Rg1 could exert its therapeutic effects on intestinal I/R injury through the Wnt/β-catenin signaling pathway and provide a novel treatment modality for intestinal I/R injury.

Mesenchymal Stem Cells Support Migration, Extracellular Matrix Invasion, Proliferation, and Survival of Endothelial Cells In Vitro

Stem Cells ◽  
2007 ◽  
Vol 25 (7) ◽  
pp. 1761-1768 ◽  
Author(s):  
Irina A. Potapova ◽  
Glenn R. Gaudette ◽  
Peter R. Brink ◽  
Richard B. Robinson ◽  
Michael R. Rosen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells

scholarly journals Three-Dimensional Aggregates Enhance the Therapeutic Effects of Adipose Mesenchymal Stem Cells for Ischemia-Reperfusion Induced Kidney Injury in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaozhi Zhao ◽  
Xuefeng Qiu ◽  
Yanting Zhang ◽  
Shiwei Zhang ◽  
Xiaoping Gu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Ischemia Reperfusion ◽  
Three Dimensional ◽  
Kidney Injury ◽  
Therapeutic Effects ◽  
Adipose Mesenchymal Stem Cells ◽  
In Vitro Data

It has been shown that administration of adipose derived mesenchymal stem cells (AdMSCs) enhanced structural and functional recovery of renal ischemia-reperfusion (IR) injury. Low engraftment of stem cells, however, limits the therapeutic effects of AdMSCs. The present study was designed to enhance the therapeutic effects of AdMSCs by delivering AdMSCs in a three-dimensional (3D) aggregates form. Microwell was used to produce 3D AdMSCs aggregates. In vitro data indicated that AdMSCs in 3D aggregates were less susceptible to oxidative and hypoxia stress induced by 200 μM peroxide and hypoxia/reoxygenation, respectively, compared with those cultured in two-dimensional (2D) monolayer. Furthermore, AdMSCs in 3D aggregates secreted more proangiogenic factors than those cultured in 2D monolayer. 2D AdMSCs or 3D AdMSCs aggregates were injected into renal cortex immediately after induction of renal IR injury. In vivo data revealed that 3D aggregates enhanced the effects of AdMSCs in recovering function and structure after renal IR injury. Improved grafted AdMSCs were observed in kidney injected with 3D aggregates compared with AdMSCs cultured in 2D monolayer. Our results demonstrated that 3D AdMSCs aggregated produced by microwell enhanced the retention and therapeutic effects of AdMSCs for renal IR injury.

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 Hypoxia Inducible Factor-1α Overexpression Enhances the Efficacy of Mesenchymal Stem Cells Derived Extracellular Vesicles for Cardiac Repair After Myocardial Infarction

2021 ◽  
Author(s):  
Qingjie Wang ◽  
Le Zhang ◽  
Zhiqin Sun ◽  
Boyu Chi ◽  
Ailin Zou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Endothelial Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiac Function ◽  
Extracellular Vesicles ◽  
Biological Effects ◽  
Hypoxia Inducible Factor ◽  
Sprague Dawley

Abstract Aims Naturally secreted extracellular vesicles (EVs) play important roles in stem-mediated cardioprotection. This study aimed to investigate the cardioprotective function and underlying mechanisms of EVs derived from HIF-1a engineered mesenchymal stem cells (MSCs) in a rat model of AMI.Methods and Results EVs isolated from HIF-1a engineered MSCs (HIF-1a-EVs) and control MSCs (MSCs-EVs) were prepared. In in vitro experiments, the EVs were incubated with cardiomyocytes and endothelial cells exposed to hypoxia and serum deprivation (H/SD); in in vivo experiments, the EVs were injected in the acutely infarcted hearts of Sprague-Dawley rats. Compared with MSCs-EVs, HIF-1a-EVs significantly inhibited the apoptosis of cardiomyocytes and enhanced angiogenesis of endothelial cells; meanwhile, HIF-1a-EVs also significantly shrunk fibrotic area and strengthened cardiac function in infarcted rats. After treatment with EVs/RGD-biotin hydrogels, we observed longer retention, higher stability in HIF-1a-EVs, and stronger cardiac function in the rats. Quantitative real-time PCR (qRT-PCR) displayed that miRNA-221-3p was highly expressed in HIF-1a-EVs. After miR-221-3p was inhibited in HIF-1a-EVs, the biological effects of HIF-1a EVs on apoptosis and angiogenesis were attenuated.Conclusion EVs released by MSCs with HIF-1a overexpression can promote the angiogenesis of endothelial cells and the apoptosis of cardiomyocytes via upregulating the expression of miR-221-3p. RGD hydrogels can enhance the therapeutic efficacy of HIF-1a engineered MSC-derived EVs.

scholarly journals Mouse Mesenchymal Stem Cell-derived Exosomal Mir-466f-3p Reverses Emt Process Through Inhibiting Akt/gsk3β Pathway via C-met in Radiation-induced Lung Injury

2022 ◽  
Author(s):  
Yi Li ◽  
Zhufu Shen ◽  
Xiao Jiang ◽  
Yuanyuan Wang ◽  
Zuozhang Yang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Lung Injury ◽  
Lung Fibrosis ◽  
Luciferase Assay ◽  
Mechanistic Study ◽  
Protective Effects ◽  
Mesenchymal Transition ◽  
Radiation Induced

Abstract Background: Radiation-induced lung fibrosis (RILF) is a common complication of thoracic radiotherapy. Alveolar epithelial cells play a crucial role in lung fibrosis via epithelial-mesenchymal transition (EMT). Exosomes derived from mesenchymal stem cells own the beneficial properties to repair and regeneration of damaged tissues, however the underlying mechanisms remain poorly understood. Methods: Mouse mesenchymal stem cells-derived exosomes (mMSCs-Exo) were isolated by differential centrifugation, and their protective effects were assessed in vivo and in vitro , respectively. EMT-associated proteins were measured via western blot assay and/or immunofluorescence staining. The miRNA expression was measured by microarray assay and qPCR. Furthermore, bioinformatics prediction with KEGG analysis, luciferase assay, and rescue experiments were performed to explore the molecular mechanism underlying miR-466f-3p. Results: mMSCs-Exos were efficiently isolated ranging from 90-150 nm with high expression of exosomal markers (CD63, TSG101, and CD9). mMSCs-Exos administration efficiently relieved radiation-induced lung injury with less collagen deposition and lower levels of IL-1β and IL-6. Meanwhile, in vitro results showed mMSCs-Exos treatment obviously reversed EMT process induced by radiation. Among enriched miRNA cargo in exosomes, miR-466f-3p was primarily responsible for the protective effects via inhibition of AKT/GSK3β pathway. Our mechanistic study further demonstrated that c-MET was the direct target of miR-466f-3p, whose restoration partially abrogated mMSCs-Exo-mediated inhibition in both EMT process and AKT/GSK3β signaling activity induced by radiation. Conclusions: Our findings indicated that exosomal miR-466f-3p derived from mMSCs may possess anti-fibrotic properties and prevent radiation-induced EMT through inhibition of AKT/GSK3β via c-MET, providing a promising therapeutic modality for radiation-induced lung fibrosis.

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