scholarly journals The Efficacy of Mesenchymal Stem Cells in Therapy of Acute Kidney Injury Induced by Ischemia-Reperfusion in Animal Models

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Tianbiao Zhou ◽  
Chunling Liao ◽  
Shujun Lin ◽  
Wenshan Lin ◽  
Hongzhen Zhong ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Animal Models ◽  
Ischemia Reperfusion ◽  
Meta Analysis ◽  
Cochrane Review ◽  
Kidney Injury ◽  
Cochrane Library ◽  
Differentiation Potential

Mesenchymal stem cells (MSCs), discovered and isolated from the bone marrow in the 1960s and with self-renewal capacity and multilineage differentiation potential, have valuable immunomodulatory abilities. Acute kidney injury (AKI) refers to rapid renal failure, which exhibits as quickly progressive decreasing excretion in few hours or days. This study was performed to assess the efficacy of MSCs in the treatment of AKI induced by ischemia-reperfusion using a meta-analysis method. A literature search using corresponding terms was performed in the following databases: Embase, Cochrane Library, PubMed, and ISI Web of Science databases up to Dec 31, 2019. Data for outcomes were identified, and the efficacy of MSCs for AKI was assessed using Cochrane Review Manager Version 5.3. Nineteen studies were eligible and recruited for this meta-analysis. MSC treatment can reduce the Scr levels at 1 day, 2 days, 3 days, 5 days, and >7 days (1 day: WMD=−0.56, 95% CI: -0.78, -0.34, P<0.00001; 2 days: WMD=−0.58, 95% CI: -0.89, -0.28, P=0.0002; 3 days: WMD=−0.65, 95% CI: -0.84, -0.45, P<0.00001; 5 days: WMD=−0.35, 95% CI: -0.54, -0.16, P=0.0003; and >7 days: WMD=−0.22, 95% CI: -0.36, -0.08, P=0.002) and can reduce the levels of BUN at 1 day, 2 days, 3 days, and 5 days (1 day: WMD=−11.72, 95% CI: -18.80, -4.64, P=0.001; 2 days: WMD=−33.60, 95% CI: -40.15, -27.05, P<0.00001; 3 days: WMD=−21.14, 95% CI: -26.15, -16.14, P<0.00001; and 5 days: WMD=−8.88, 95% CI: -11.06, -6.69, P<0.00001), and it also can reduce the levels of proteinuria at 3 days and >7 days and alleviate the renal damage in animal models of AKI. In conclusion, MSCs might be a promising therapeutic agent for AKI induced by ischemia-reperfusion.

scholarly journals Bone mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury

2020 ◽  
Author(s):  
song zhou ◽  
Yu-ming Qiao ◽  
Yong-guang Liu ◽  
Ding Liu ◽  
Jian-min Hu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Early Death ◽  
Underlying Mechanism ◽  
Bone Mesenchymal Stem Cells ◽  
P53 Expression ◽  
Inflammatory Microenvironment

Abstract Background Mesenchymal stem cells (MSCs) represent a promising treatment option for acute kidney injury (AKI).The main drawbacks of MSC therapy including the lack of specific homing following systemic infusion and early death of the cells in the inflammatory microenvironment, directly affect the therapeutic efficacy of MSCs. Erythropoietin (EPO)-preconditioning promotes the therapeutic effect of the MSCs, although the underlying mechanism remains unknown. In this study, we sought to investigate the efficacy and mechanism of EPO on bone marrow mesenchymal stem cells (BMSCs) for the treatment of AKI.Results We found that incubation of BMSCs with ischemia/reperfusion(I/R)-induced AKI kidney homogenate supernatant (KHS) caused apoptosis in the BMSCs, which was decreased following EPO pretreatment indicating that EPO protected the cells from apoptosis. Further, we found that EPO upregulated SIRT1 and Bcl-2 expression, and downregulated p53 expression. The EPO-mediated anti-apoptotic mechanism in pretreated BMSCs may be mediated though the SIRT1 pathway. In a rat AKI model, our data showed that 24 h following intravenous infusion, GFP-BMSCs were predominantly in the lungs. However, EPO pretreatment reduced the lung entrapment of BMSCs, and increased the distribution of the BMSCs to the target organs. AKI rats infused with EPO-BMSCs had significantly lower levels of serum IL-1β and TNF-a and significantly higher level of IL-10 compared to rats infused with BMSCs. The administration of EPO-BMSCs after reperfusion was more effective in reducing serum creatinine, blood urea nitrogen, and pathological scores in the I/R-AKI rats than BMSCs.Conclusions Our data suggest that EPO pretreatment enhances the efficacy of BMSCs in improving renal function and pathological presentation in I/R-AKI rats.

scholarly journals Bone Marrow-Derived Mesenchymal Stem Cells Ameliorate Sepsis-Induced Acute Kidney Injury by Promoting Mitophagy of Renal Tubular Epithelial Cells via the SIRT1/Parkin Axis

2021 ◽  
Vol 12 ◽  
Author(s):  
Jun Guo ◽  
Rong Wang ◽  
Donghai Liu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Epithelial Cells ◽  
Kidney Injury ◽  
Tubular Epithelial Cells ◽  
Renal Tubular Epithelial Cells ◽  
Differentiation Potential ◽  
Renal Tubular

Sepsis is a common risk factor for acute kidney injury (AKI). Bone marrow-derived mesenchymal stem cells (BMSCs) bear multi-directional differentiation potential. This study explored the role of BMSCs in sepsis-induced AKI (SI-AKI). A rat model of SI-AKI was established through cecal ligation and perforation. The SI-AKI rats were injected with CM-DiL-labeled BMSCs, followed by evaluation of pathological injury of kidney tissues and kidney injury-related indicators and inflammatory factors. HK-2 cells were treated with lipopolysaccharide (LPS) to establish SI-SKI model in vitro. Levels of mitochondrial proteins, autophagy-related proteins, NLRP3 inflammasome-related protein, and expressions of Parkin and SIRT1 in renal tubular epithelial cells (RTECs) of kidney tissues and HK-2 cells were detected. The results showed that BMSCs could reach rat kidney tissues and alleviate pathological injury of SI-SKI rats. BMSCs inhibited inflammation and promoted mitophagy of RTECs and HK-2 cells in rats with SI-AKI. BMSCs upregulated expressions of Parkin and SIRT1 in HK-2 cells. Parkin silencing or SIRT1 inhibitor reversed the promoting effect of BMSCs on mitophagy. BMSCs inhibited apoptosis and pyroptosis of RTECs in kidney tissues by upregulating SIRT1/Parkin. In conclusion, BMSCs promoted mitophagy and inhibited apoptosis and pyroptosis of RTECs in kidney tissues by upregulating SIRT1/Parkin, thereby ameliorating SI-AKI.

scholarly journals PINK1 Kinase Enhances the Repair Effects of Bone Marrow Mesenchymal Stem Cells on Renal Ischemia/Reperfusion-Induced Acute Kidney Injury in Mice

2022 ◽  
Author(s):  
Chenyu Lin ◽  
Wen Chen ◽  
Yong Han ◽  
Yujie Sun ◽  
Xiaoqiong Zhao ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Stress Response ◽  
Immune Cells ◽  
Peripheral Blood ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Short Period ◽  
Injured Kidney

Abstract Background: Acute kidney injury (AKI) is a common severe acute syndrome caused by multiple causes, which is characterized by a rapid decline of renal function in a short period. Bone mesenchymal stem cells (BMSCs) are effective in the treatment of AKI. However, it remains unclear about the mechanism of their beneficial effects. PENT-induced kinase 1 (PINK1) may play an important role in the kidney tissue repair. In this study, an endeavor would be made to explore the enhancing effect of PINK1 overexpression on the repair of AKI through BMSCs. Methods: In this study, the ischemia/reperfusion-induced acute kidney injury (IRI-AKI) in mice and the hypoxia-reoxygenation model of cells were established, and the indexes were detected by pathology and immunology experimental.Results: After ischemia/reperfusion, compared with the BMSCs group, the OE PINK1 group had a decreased expression of BUN, the mitigated renal fibrosis , the reduced tissue damage degree. Overexpressed PINK1 could decrease the inflammatory reaction of injured kidney tissues in IRI-AKI mice, the decreased expression of IL-10 in peripheral blood serum; and regulate the distribution of immune cells in the kidney during IRI, the decreased infiltration of lymphocytes, the increased infiltration of macrophages; and reduce the stress response of BMSCs under hypoxia and inflammation; and enhance the stress response of BMSCs to renal tubular epithelial cells(RTECs) under hypoxia and inflammation, the decreased apoptosis rate of RTECs, the decreased release of TNF-α in the cell supernatant, and the decreased proliferation of PBMCs in peripheral blood after hypoxia and reoxygenation; and regulate the autophagy of BMSCs in kidney tissues with IRI-AKI to better repair the injured kidney tissues, the increased expression of LC3-B related to autophagy and the decreased expression of mTOR.Conclusions: In this study, PINK1 overexpression enhances the repair effect of BMSCs on IRI-AKI, and the distribution of injured renal immune cells during IRI regulation by BMSCs. Besides, PINK1 enhances BMSCs and their resistance to the stress response of RTECs under hypoxia and inflammation. In addition, it regulates mitophagy during IRI-AKI. The findings of this study provide a new direction and target for the repair of IRI-AKI through BMSCs.

scholarly journals Bone marrow derived mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury

2020 ◽  
Author(s):  
song zhou ◽  
Yu-ming Qiao ◽  
Yong-guang Liu ◽  
Ding Liu ◽  
Jian-min Hu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Underlying Mechanism ◽  
P53 Expression ◽  
Inflammatory Microenvironment ◽  
Apoptotic Effect

Abstract Background Mesenchymal stem cells (MSCs) represent a promising treatment option for acute kidney injury (AKI). The main drawbacks of MSCs therapy, including the lack of specific homing after systemic infusion and early cell death in the inflammatory microenvironment, directly affect the therapeutic efficacy of MSCs. Erythropoietin (EPO)-preconditioning of MSCs promotes their therapeutic effect; however, the underlying mechanism remains unknown. In this study, we sought to investigate the efficacy and mechanism of EPO in bone marrow derived mesenchymal stem cells (BMSCs) for AKI treatment. Results We found that incubation of BMSCs with ischemia/reperfusion(I/R)-induced AKI kidney homogenate supernatant (KHS) caused apoptosis in BMSCs, which was decreased by EPO pretreatment, indicating that EPO protected the cells from apoptosis. Further, we showed that EPO up-regulated SIRT1 and Bcl-2 expression and down-regulated p53 expression. This effect was partially reversed by SIRT1 siRNA intervention. The anti-apoptotic effect of EPO in pretreated BMSCs may be mediated through the SIRT1 pathway. In a rat AKI model, 24 h after intravenous infusion, GFP-BMSCs were predominantly located in the lungs. However, EPO pretreatment reduced the lung entrapment of BMSCs and increased their distribution in the target organs. AKI rats infused with EPO-BMSCs had significantly lower levels of serum IL-1β and TNF-α, and a significantly higher level of IL-10 as compared to rats infused with untreated BMSCs. The administration of EPO-BMSCs after reperfusion reduced serum creatinine, blood urea nitrogen, and pathological scores in I/R-AKI rats more effectively than BMSCs treatment did. Conclusions Our data suggest that EPO pretreatment enhances the efficacy of BMSCs to improve the renal function and pathological presentation of I/R-AKI rats.

scholarly journals Mesenchymal Stem Cells for the Treatment of Intestinal Ischemia-reperfusion Injury: a Protocol of Systematic Review and Meta-analysis of Animal Models

2021 ◽  
Author(s):  
Guangru Zhang ◽  
Shenghong Suo ◽  
Zhenzhen Liu ◽  
Disheng Liu ◽  
Zhiyu Zhao ◽  
...  
Keyword(s):  
Systematic Review ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Animal Models ◽  
Intestinal Ischemia ◽  
Ischemia Reperfusion ◽  
Meta Analysis ◽  
Mean Difference ◽  
Clinical Event ◽  
Intestinal Ischemia Reperfusion

Abstract Introduction: Intestinal ischemia-reperfusion (I/R) injury is a common clinical event. Mesenchymal stem cells (MSCs) have been widely used to repair intestinal injury in animal models. However, the effects of MSCs on intestinal I/R injury therapy remain unclear. Thus, we will perform a systematic review and meta-analysis of controlled trials to evaluate the efficacy of MSCs in animal models of intestinal I/R injury.Methods and analysis: We will search PubMed, Web of Science, Embase, Cochrane Library, Science Citation Index, China National Knowledge Information database, Wanfang Database, and the Chinese Scientific and Technological Journal Database in May 2021. We will include studies that evaluate the two different interventions for target MSCs to be maintained for the degree of histopathologic changes, mortality rate of rats, tumour necrosis factor α, and diamine oxidase. Two reviewers will independently screen titles and abstracts, perform a full article review, and extract study data. We will also use the SYRCLE tool to assess the risk of bias in the included studies. Furthermore, a random-effects meta-analysis will be conducted. Dichotomous and continuous outcomes will be analysed using risk ratios with 95% confidence intervals (CIs) and weighted mean difference with 95% CIs, respectively. For outcomes where different scales or different measurement methods have been used, the standardised mean difference will be applied. Subgroup and sensitivity analyses will be performed to explore the heterogeneity. Stata (version 12.0, Stata Corp, College Station, Texas, USA) will be used to analyse and pool the individual research results.Ethics and dissemination: This systematic review and meta-analysis does not require an ethical approval because no human beings are involved. We aim to publish this systematic review in a peer-reviewed journal.PROSPERO registration number: CRD42021231826

scholarly journals Bone mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury

2020 ◽  
Author(s):  
song zhou ◽  
Yu-ming Qiao ◽  
Yong-guang Liu ◽  
Ding Liu ◽  
Jian-min Hu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Underlying Mechanism ◽  
Bone Mesenchymal Stem Cells ◽  
P53 Expression ◽  
Inflammatory Microenvironment ◽  
Marrow Mesenchymal Stem Cells

Abstract Background: Mesenchymal stem cells (MSCs) represent a promising treatment option for acute kidney injury (AKI). The main drawbacks of MSCs therapy, including the lack of specific homing after systemic infusion and early cell death in the inflammatory microenvironment, directly affect the therapeutic efficacy of MSCs. Erythropoietin (EPO)-preconditioning of MSCs promotes their therapeutic effect; however, the underlying mechanism remains unknown. In this study, we sought to investigate the efficacy and mechanism of EPO in bone marrow mesenchymal stem cells (BMSCs) for AKI treatment.Results: We found that incubation of BMSCs with ischemia/reperfusion(I/R)-induced AKI kidney homogenate supernatant (KHS) caused apoptosis in BMSCs, which was decreased by EPO pretreatment, indicating that EPO protected the cells from apoptosis. Further, we showed that EPO up-regulated SIRT1 and Bcl-2 expression and down-regulated p53 expression. This effect was partially reversed by SIRT1 siRNA intervention. The anti-apoptotic effect of EPO in pretreated BMSCs may be mediated through the SIRT1 pathway. In a rat AKI model, 24 h after intravenous infusion, GFP-BMSCs were predominantly located in the lungs. However, EPO pretreatment reduced the lung entrapment of BMSCs and increased their distribution in the target organs. AKI rats infused with EPO-BMSCs had significantly lower levels of serum IL-1β and TNF-α, and a significantly higher level of IL-10 as compared to rats infused with untreated BMSCs. The administration of EPO-BMSCs after reperfusion reduced serum creatinine, blood urea nitrogen, and pathological scores in I/R-AKI rats more effectively than BMSCs treatment did.Conclusions: Our data suggest that EPO pretreatment enhances the efficacy of BMSCs to improve the renal function and pathological presentation of I/R-AKI rats.

scholarly journals Bone marrow derived mesenchymal stem cells pretreated with erythropoietin accelerate the repair of acute kidney injury

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Song Zhou ◽  
Yu-ming Qiao ◽  
Yong-guang Liu ◽  
Ding Liu ◽  
Jian-min Hu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Underlying Mechanism ◽  
P53 Expression ◽  
Inflammatory Microenvironment ◽  
Apoptotic Effect

Abstract Background Mesenchymal stem cells (MSCs) represent a promising treatment option for acute kidney injury (AKI). The main drawbacks of MSCs therapy, including the lack of specific homing after systemic infusion and early cell death in the inflammatory microenvironment, directly affect the therapeutic efficacy of MSCs. Erythropoietin (EPO)-preconditioning of MSCs promotes their therapeutic effect, however, the underlying mechanism remains unknown. In this study, we sought to investigate the efficacy and mechanism of EPO in bone marrow derived mesenchymal stem cells (BMSCs) for AKI treatment. Results We found that incubation of BMSCs with ischemia/reperfusion(I/R)-induced AKI kidney homogenate supernatant (KHS) caused apoptosis in BMSCs, which was decreased by EPO pretreatment, indicating that EPO protected the cells from apoptosis. Further, we showed that EPO up-regulated silent information regulator 1 (SIRT1) and Bcl-2 expression and down-regulated p53 expression. This effect was partially reversed by SIRT1 siRNA intervention. The anti-apoptotic effect of EPO in pretreated BMSCs may be mediated through the SIRT1 pathway. In a rat AKI model, 24 h after intravenous infusion, GFP-BMSCs were predominantly located in the lungs. However, EPO pretreatment reduced the lung entrapment of BMSCs and increased their distribution in the target organs. AKI rats infused with EPO-BMSCs had significantly lower levels of serum IL-1β and TNF-α, and a significantly higher level of IL-10 as compared to rats infused with untreated BMSCs. The administration of EPO-BMSCs after reperfusion reduced serum creatinine, blood urea nitrogen, and pathological scores in I/R-AKI rats more effectively than BMSCs treatment did. Conclusions Our data suggest that EPO pretreatment enhances the efficacy of BMSCs to improve the renal function and pathological presentation of I/R-AKI rats.

Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury

2007 ◽  
Vol 292 (5) ◽  
pp. F1626-F1635 ◽  
Author(s):  
Florian Tögel ◽  
Kathleen Weiss ◽  
Ying Yang ◽  
Zhuma Hu ◽  
Ping Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Kidney Injury ◽  
Blood Flow ◽  
Mesenchymal Stem Cells ◽  
Conditioned Medium ◽  
Expression Profiles ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Cell Phenotype ◽  
Paracrine Actions

Acute kidney injury (AKI) is a major clinical problem in which a critical vascular, pathophysiological component is recognized. We demonstrated previously that mesenchymal stem cells (MSC), unlike fibroblasts, are significantly renoprotective after ischemia-reperfusion injury and concluded that this renoprotection is mediated primarily by paracrine mechanisms. In this study, we investigated whether MSC possess vasculoprotective activity that may contribute, at least in part, to an improved outcome after ischemia-reperfusion AKI. MSC-conditioned medium contains VEGF, HGF, and IGF-1 and augments aortic endothelial cell (EC) growth and survival, a response not observed with fibroblast-conditioned medium. MSC and EC share vasculotropic gene expression profiles, as both form capillary tubes in vitro on Matrigel alone or in cooperation without fusion. MSC undergo differentiation into an endothelial-like cell phenotype in culture and develop into vascular structures in vivo. Infused MSC were readily detected in the kidney early after reflow but were only rarely engrafted at 1 wk post-AKI. MSC attached in the renal microvascular circulation significantly decreased apoptosis of adjacent cells. Infusion of MSC immediately after reflow in severe ischemia-reperfusion AKI did not improve renal blood flow, renovascular resistance, or outer cortical blood flow. These data demonstrate that the unique vasculotropic, paracrine actions elicited by MSC play a significant renoprotective role after AKI, further demonstrating that cell therapy has promise as a novel intervention in AKI.

Sign in / Sign up

Export Citation Format

Share Document