scholarly journals The protective effect of human adiposederived mesenchymal stem cells on cisplatin-induced nephrotoxicity is dependent on their level of expression of heme oxygenase-1

2020 ◽  
Vol 18 ◽  
pp. 205873922093456
Author(s):  
Hyun Seop Cho ◽  
Ha Nee Jang ◽  
Myeong Hee Jung ◽  
Si Jung Jang ◽  
Sang-Ho Jeong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Heme Oxygenase ◽  
Therapeutic Efficacy ◽  
Therapeutic Potential ◽  
Expression Level ◽  
Heme Oxygenase 1 ◽  
Sprague Dawley ◽  
Migration Ability ◽  
Induced Apoptosis

The therapeutic efficacy of adipose mesenchymal stem cells (Ad-MSCs) for acute kidney injury (AKI) has been investigated extensively, and the anti-apoptotic, anti-inflammatory, and proangiogenic effects of heme oxygenase-1 (HO-1) reportedly ameliorate AKI. We hypothesized that the therapeutic efficacy of Ad-MSCs is dependent on their expression level of HO-1. The viability and migration ability of cisplatin-treated human renal proximal tubular epithelial cells were assessed. Sprague–Dawley rats were divided into control, cisplatin (10 mg/kg), and cisplatin plus Ad MSCs (with high and low HO-1 expression) groups. The HO-1 expression level in hAd-MSCs increased with increasing passage number, peaking at passage 4 and decreasing thereafter. The viability and migratory ability of hAd-MSCs with high HO-1 expression were greater than those of hAd-MSCs with low HO-1 expression. Renal tubular toxicity in cisplatin-treated rats was ameliorated by administration of hAd-MSCs with high HO-1 expression, although the levels of blood urea nitrogen and serum creatinine did not differ according to the level of HO-1 expression. The magnitude of reactive oxygen species induced DNA damage was lower in hAd-MSCs with high HO-1 expression than in those with low HO-1 expression. Administration of hAd-MSCs significantly suppressed cisplatin induced apoptosis. Also, hAd-MSCs with high HO-1 expression were more resistant to cisplatin-induced apoptosis than were those with low HO-1 expression. hAd MSCs with high HO-1 expression have therapeutic potential for cisplatin induced nephrotoxicity, based on our in vitro and in vivo results. These findings will facilitate the development of novel therapeutic strategies for cisplatin-induced AKI.

Mesenchymal stem cells increase heme oxygenase 1-activated autophagy in treatment of acute liver failure

2019 ◽  
Vol 508 (3) ◽  
pp. 682-689 ◽  
Author(s):  
Yue Wang ◽  
Jing-lin Wang ◽  
Hu-cheng Ma ◽  
Zhen-ting Tang ◽  
Hao-ran Ding ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Heme Oxygenase ◽  
Heme Oxygenase 1

Directions for Enhancement of the Therapeutic Efficacy of Mesenchymal Stem Cells in Different Neurodegenerative and Cardiovascular Diseases: Current Status and Future Perspectives

2021 ◽  
Vol 16 ◽  
Author(s):  
Lamiaa A. Ahmed ◽  
Khaled F. Al-Massri
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiovascular Diseases ◽  
Neurodegenerative Disorders ◽  
Therapeutic Efficacy ◽  
Therapeutic Potential ◽  
Current Status ◽  
Therapeutic Effects ◽  
Paracrine Factors ◽  
Apoptotic Effects

: Mesenchymal stem cells (MSCs) have shown promising therapeutic effects in a wide variety of medical conditions including neurodegenerative disorders and cardiovascular diseases. Although preliminary research has emphasized the ability of MSCs to engraft at sites of injury, several studies have revealed that MSCs mediate their effects through release of various paracrine factors, and through their antioxidant, anti-inflammatory, immunomodulatory, and anti-apoptotic effects. However, the clinical implications of MSCs application are limited due to their low survival rate in conditions of inflammation, oxidative stress, and nutrient restriction in damaged areas. Furthermore, the function of isolated MSCs is usually affected by the patient’s health. Therefore, it is necessary to develop new methods to enhance the therapeutic efficacy of MSCs under pathophysiological conditions. This review provides an overview of the general properties of MSCs, their therapeutic potential in neurodegenerative disorders such as Alzheimer disease, Parkinson disease, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington disease, as well as cardiovascular diseases such as myocardial infarction, diabetic cardiomyopathy, and dilated cardiomyopathy, and their related mechanisms. In addition, this review also discusses potential problems and side effects, as well as current and future directions for improvement of MSCs therapy and their implications and applications.

Adiponectin Improves Therapeutic Efficacy of Mesenchymal Stem Cells by Enhancing Their Engraftment and Survival in Peri-infarct Myocardium Through AMPK Pathway

2020 ◽  
Author(s):  
Xiaqiu Tian ◽  
Xiao-Song Qian ◽  
Hong Wang ◽  
Yue-Jin Yang
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Smooth Muscle ◽  
Cardiac Function ◽  
Therapeutic Efficacy ◽  
Therapeutic Potential ◽  
Cardiac Repair ◽  
Heart Catheterization ◽  
Cell Marker ◽  
Ampk Pathway

Abstract Background: Poor viability of transplanted mesenchymal stem cells (MSCs)within the ischemic heart has limited their therapeutic potential for cardiac repair. We have recently demonstrated that adiponectin (APN) inhibits the apoptosis of MSCs under hypoxia and serum-deprivation conditionsin vitro. This study investigated whether APN could promote the survival of MSCs in vivoand further contribute to cardiac repair after acute myocardial infarction (AMI), via the adenosine monophosphate-activated protein kinase(AMPK)pathway. Methods: Rats were randomized into six groups: the Sham, AMI control, and 4 other groups that were subjected to AMI followed by treatment with MSCs, APN, APN + MSCs and APN + MSCs + AMPK inhibitor. MSCs labeled with CM-Dil were injected through the jugular vein in 24 hours post AMI. At 4-week after AMI, engraftment of MSCs to the peri-infarct myocardium was evaluated. Cardiac function was assessed using echocardiography and left heart catheterization. Apoptosis and fibrosis were measured with TUNEL and Masson’s trichrome staining. H&E staining and immunohistochemistry against CD 68 and CD 206 were performed to assess the infiltration of inflammatory cells. Expressions of inflammatory cytokines were determined with ELISA. Immunostaining against smooth muscle cell marker α-smooth-muscle actin (α-SMA) and endothelial cell marker CD31 antibodies were performed to assess arteriogenesis and angiogenesis. Results: APN treatment significantly enhanced the engraftment and survival rate of transplanted MSCs accompanied by markedly improved cardiac function and decreased infarct size at 4-week after AMI. Combined administration of APN and MSCs markedly suppressed inflammatory response, specifically promoted shift of infiltrated macrophages to anti-inflammatory phenotype.Combined administration of APN and MSCs also significantly inhibited cardiomyocytes apoptosis, while increased arteriogenesis and angiogenesis in the peri-infarct myocardium when compared with MSCs transplantation alone. These protective effects of APN were associated with AMPK phosphorylation, which were almost completely reversed by AMPK pathway inhibitor. Conclusions: Our results demonstrated that APN could improve the survival and therapeutic efficacy of transplanted MSCs after AMI through AMPK activation.Our study suggests the potential application of APN for improvement of stem cell-based heart repair and regeneration.

scholarly journals Overexpression of Heme Oxygenase-1 in Mesenchymal Stem Cells Augments Their Protection on Retinal Cells In Vitro and Attenuates Retinal Ischemia/Reperfusion Injury In Vivo against Oxidative Stress

2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Li Li ◽  
GaiPing Du ◽  
DaJiang Wang ◽  
Jin Zhou ◽  
Guomin Jiang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Heme Oxygenase ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Retinal Ischemia ◽  
Heme Oxygenase 1

Retinal ischemia/reperfusion (I/R) injury, involving several ocular diseases, seriously threatens human ocular health, mainly treated by attenuating I/R-induced oxidative stress. Currently, mesenchymal stem cells (MSCs) could restore I/R-injured retina through paracrine secretion. Additionally, heme oxygenase-1 (HO-1) could ameliorate oxidative stress and thus retinal apoptosis, but the expression of HO-1 in MSC is limited. Here, we hypothesized that overexpression of HO-1 in MSC (MSC-HO-1) may significantly improve their retina-protective potentials. The overexpression of HO-1 in MSC was achieved by lentivirus transduction. Then, MSC or MSC-HO-1 was cocultured with retinal ganglion cells (RGC-5) in H2O2-simulated oxidative condition and their protection on RGC-5 was systemically valuated in vitro. Compared with MSC, MSC-HO-1 significantly attenuated H2O2-induced injury of RGC-5, including decrease in cellular ROS level and apoptosis, activation of antiapoptotic proteins p-Akt and Bcl-2, and blockage of proapoptotic proteins cleaved caspase 3 and Bax. In retinal I/R rats model, compared with control MSC, MSC-HO-1-treated retina significantly retrieved its structural thickness, reduced cell apoptosis, markedly attenuated retinal oxidative stress level, and largely regained the activities of typical antioxidant enzymes, SOD and CAT. Therefore, it could be concluded that overexpression of HO-1 provides a promising strategy to enhance the MSC-based therapy for I/R-related retinal injury.

scholarly journals Improvement of Liver Transplantation Outcome by Heme Oxygenase-1-Transduced Bone Marrow Mesenchymal Stem Cells in Rats

2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Bin Wu ◽  
Hong-Li Song ◽  
Yang Yang ◽  
Ming-Li Yin ◽  
Bo-Ya Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Liver Transplantation ◽  
Mesenchymal Stem Cells ◽  
Heme Oxygenase ◽  
Transforming Growth Factor ◽  
The Other ◽  
Heme Oxygenase 1 ◽  
Immunomodulatory Effects ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMMSCs) exert immunosuppressive activity in transplantation, and heme oxygenase-1 (HO-1) enhances their immunomodulatory effects. The aim of this study was to determine whether HO-1-transduced BMMSCs (HO-1/MSCs) improve rat liver transplantation (LTx) outcomes. Orthotopic LTx rejection models were treated with HO-1/MSCs, BMMSCs, HO-1, or normal saline, respectively. Our results showed a significant improvement in survival rates in the HO-1/BMMSCs group compared to the control groups. At all time points, liver function marker levels in the HO-1/MSCs group were significantly lower than in the other three groups; on POD 1, 7, and 14, the degree of rejection and apoptotic cells was significantly less in the HO-1/MSCs group than in the other three groups. Interleukin- (IL-) 10 and transforming growth factor-βlevels were significantly increased, while IL-2, IL-6, IL-17, IL-23, tumor necrosis factor-α, and interferon-γlevels were significantly decreased in the HO-1/MSCs group when compared to the other groups. Splenocyte Tregs were significantly increased by HO-1/MSCs compared with controls on POD 3, 5, 7, 10, 14, and 28. Summarily, we provide evidence that HO-1/MSCs improved allogeneic LTx outcomes by attenuating inflammatory responses and acute cellular rejection, as well as enhanced immunomodulatory effects compared with BMMSCs.

scholarly journals Effects of combined mesenchymal stem cells and heme oxygenase-1 therapy on cardiac performance☆

2008 ◽  
Vol 34 (4) ◽  
pp. 850-856 ◽  
Author(s):  
Bin Zeng ◽  
Honglei Chen ◽  
Chengang Zhu ◽  
Xiaofeng Ren ◽  
Guosheng Lin ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Heme Oxygenase ◽  
Cardiac Performance ◽  
Heme Oxygenase 1
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