scholarly journals Therapeutic Potential of Mesenchymal Stem Cells in a Pre-Clinical Model of Diabetic Kidney Disease and Obesity

2021 ◽  
Vol 22 (4) ◽  
pp. 1546
Author(s):  
Christian Sávio-Silva ◽  
Poliana E. Soinski-Sousa ◽  
Antônio Simplício-Filho ◽  
Rosana M. C. Bastos ◽  
Stephany Beyerstedt ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Dependent Manner ◽  
Glomerular Mesangial Cells ◽  
Diabetic Kidney ◽  
Ros Accumulation

Diabetic kidney disease (DKD) is a worldwide microvascular complication of type 2 diabetes mellitus (T2DM). From several pathological mechanisms involved in T2DM-DKD, we focused on mitochondria damage induced by hyperglycemia-driven reactive species oxygen (ROS) accumulation and verified whether mesenchymal stem cells (MSCs) anti-oxidative, anti-apoptotic, autophagy modulation, and pro-mitochondria homeostasis therapeutic potential curtailed T2DM-DKD progression. For that purpose, we grew immortalized glomerular mesangial cells (GMCs) in hyper glucose media containing hydrogen peroxide. MSCs prevented these cells from apoptosis-induced cell death, ROS accumulation, and mitochondria membrane potential impairment. Additionally, MSCs recovered GMCs’ biogenesis and mitophagy-related gene expression that were downregulated by stress media. In BTBRob/ob mice, a robust model of T2DM-DKD and obesity, MSC therapy (1 × 106 cells, two doses 4-weeks apart, intra-peritoneal route) led to functional and structural kidney improvement in a time-dependent manner. Therefore, MSC-treated animals exhibited lower levels of urinary albumin-to-creatinine ratio, less mesangial expansion, higher number of podocytes, up-regulation of mitochondria-related survival genes, a decrease in autophagy hyper-activation, and a potential decrease in cleaved-caspase 3 expression. Collectively, these novel findings have important implications for the advancement of cell therapy and provide insights into cellular and molecular mechanisms of MSC-based therapy in T2DM-DKD setting.

scholarly journals Effects of Mesenchymal Stem Cells Therapy on Cardiovascular Risk Factors in Experimental Diabetic Kidney Disease

2020 ◽  
Vol 7 ◽  
pp. 205435812095742
Author(s):  
Einas Nagib Hussein ◽  
Gehane M. Hamed ◽  
Ansam A. Seif ◽  
Mona A. Ahmed ◽  
Fatma Abd Elkarim Abu Zahra
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Cardiovascular Risk ◽  
Blood Glucose ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Atherogenic Index ◽  
Diabetic Kidney

Background: Diabetic kidney disease (DKD) is a progressive kidney disease and a leading cause of end-stage renal disease (ESRD). Diabetic kidney disease has been strongly associated with increased risk of cardiovascular morbidity and mortality. Despite their susceptibility to cardiovascular diseases (CVDs), patients with DKD are less likely to receive appropriate cardiovascular risk modification as they are generally excluded from major cardiovascular trials. Awareness of vulnerability of these patients necessitates investigating potential interventions that would lessen their risk of adverse outcomes. Objectives: This study aimed to explore the effect of bone marrow–derived mesenchymal stem cells (MSCs) in modulating cardiovascular risk factors that develop with the progression of DKD. Methods: A total of 60 adult female albino rats were allocated into 3 groups: control group, untreated DKD group, and mesenchymal stem cells–treated diabetic kidney disease (MSCs-DKD) group. Blood pressure, blood glucose level, lipid profile, and atherogenic index were used to assess cardiovascular risk. All rats were killed and subjected to in vitro aortic reactivity studies 8 weeks after induction of diabetes. The MSCs-DKD rats received a single intravenous injection of MSCs 4 weeks after diabetes induction. Results: Mesenchymal stem cells injection significantly decreased blood pressure, atherogenic index, and blood glucose compared with untreated rats. The MSCs-DKD aorta also exhibited significant enhancement of vascular reactivity parameters despite absence of improvement in kidney function. These findings conformed to tracked MSCs, which were found residing in aortic and pancreatic tissues and absent in kidneys. Conclusions: Mesenchymal stem cells hold hope of improving cardiovascular risk and mortality in patients with DKD, particularly those deteriorating to ESRD.

scholarly journals Sulodexide Protects Renal Tubular Epithelial Cells from Oxidative Stress-Induced Injury via Upregulating Klotho Expression at an Early Stage of Diabetic Kidney Disease

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yu Ning Liu ◽  
Jingwei Zhou ◽  
Tingting Li ◽  
Jing Wu ◽  
Shu Hua Xie ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Kidney Disease ◽  
Epithelial Cells ◽  
Diabetic Kidney Disease ◽  
Early Stage ◽  
Collaborative Study ◽  
Oxidative Activity ◽  
Dependent Manner ◽  
Diabetic Kidney ◽  
Collaborative Study Group

The hypoalbuminuric effect of sulodexide (SDX) on diabetic kidney disease (DKD) was suggested by some clinical trials but was denied by the Collaborative Study Group. In this study, the diabetic rats were treated with SDX either from week 0 to 24 or from week 13 to 24. We found that 24-week treatment significantly decreased the urinary protein and HAVCR1 excretion, inhibited the interstitial expansion, and downregulated the renal cell apoptosis and interstitial fibrosis. Renoprotection was also associated with a reduction in renocortical/urinary oxidative activity and the normalization of renal klotho expression. However, all of these actions were not observed when SDX was administered only at the late stage of diabetic nephropathy (from week 13 to 24). In vitro, advanced glycation end products (AGEs) dose-dependently enhanced the oxidative activity but lowered the klotho expression in cultured proximal tubule epithelial cells (PTECs). Also, H2O2 could downregulate the expression of klotho in a dose-dependent manner. However, overexpression of klotho reduced the HAVCR1 production and the cellular apoptosis level induced by AGEs or H2O2. Our study suggests that SDX may prevent the progression of DKD at the early stage by upregulating renal klotho expression, which inhibits the tubulointerstitial injury induced by oxidative stress.

The concurrent therapeutic potential of adipose-derived mesenchymal stem cells on Gentamycin-induced hepatorenal toxicity in rats

2021 ◽  
Vol 16 ◽  
Author(s):  
Mohamed A Rawash ◽  
Ayman Saber Mohamed ◽  
Emad M El-Zayat
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Uric Acid ◽  
Stem Cell ◽  
Kidney Disease ◽  
Therapeutic Potential ◽  
Daily Injection ◽  
Adipose Mesenchymal Stem Cells ◽  
Liver And Kidney ◽  
Therapy Option

Background: Adipose mesenchymal stem cells (AMSCs) are a type of stem cell employed to repair damaged organs. This study aimed to see how effective AMSCs are at treating gentamycin-induced hepatorenal damage in rats. Methods: 18 male Wister rats were assigned into three groups; control, Gentamycin (GM), and GM+AMSCs. GM induced hepatorenal toxicity through daily injection (100 mg/kg, i.p.) for eight days. On day 9, AMSC (106 cells/ml/rat) was injected intravenously. Results : Creatinine, urea, uric acid, AST, ALP, ALT, TNF-, and MDA levels decreased, whereas IL-10, GSH, and CAT levels increased, indicating the therapeutic potency of intravenous injection AMSCs. Conclusion: The current study demonstrated the simultaneous therapeutic efficacy of adipose mesenchymal stem cells on the liver and kidney in the treatment of Gentamycin-induced hepatotoxicity. These data show that AMSCs could be a feasible therapy option for liver and kidney disease.

scholarly journals MicroRNAs in Diabetic Kidney Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-11 ◽  
Author(s):  
Rong Li ◽  
Arthur C. K. Chung ◽  
Xueqing Yu ◽  
Hui Y. Lan
Keyword(s):  
Kidney Disease ◽  
Messenger Rna ◽  
Diabetic Kidney Disease ◽  
Target Genes ◽  
Therapeutic Potential ◽  
Expression Patterns ◽  
Diagnostic Tools ◽  
Diabetic Kidney ◽  
Functional Studies ◽  
Gene Expression Studies

Rapid growth of diabetes and diabetic kidney disease exerts a great burden on society. Owing to the lack of effective treatments for diabetic kidney disease, treatment relies on drugs that either reduces its progression or involve renal replacement therapies, such as dialysis and kidney transplantation. It is urgent to search for biomarkers for early diagnosis and effective therapy. The discovery of microRNAs had lead to a new era of post-transcriptional regulators of gene expression. Studies from cells, experimental animal models and patients under diabetic conditions demonstrate that expression patterns of microRNAs are altered during the progression of diabetic kidney disease. Functional studies indicate that the ability of microRNAs to bind 3′ untranslated region of messenger RNA not only shows their capability to regulate expression of target genes, but also their therapeutic potential to diabetic kidney disease. The presence of microRNAs in plasma, serum, and urine has been shown to be possible biomarkers in diabetic kidney disease. Therefore, identification of the pathogenic role of microRNAs possesses an important clinical impact in terms of prevention and treatment of progression in diabetic kidney disease because it allows us to design novel and specific therapies and diagnostic tools for diabetic kidney disease.

scholarly journals Exercise Ameliorates Diabetic Kidney Disease in Type 2 Diabetic Fatty Rats

Antioxidants ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1754
Author(s):  
Itaru Monno ◽  
Yoshio Ogura ◽  
Jing Xu ◽  
Daisuke Koya ◽  
Munehiro Kitada
Keyword(s):  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Kidney Injury ◽  
Male Rats ◽  
Fatty Acid Binding ◽  
Diabetic Kidney ◽  
Beneficial Effects ◽  
Type 2 Diabetic

Lifestyle improvement, including through exercise, has been recognized as an important mode of therapy for the suppression of diabetic kidney disease (DKD). However, the detailed molecular mechanisms by which exercise exerts beneficial effects in the suppression of DKD have not yet been fully elucidated. In this study, we investigate the effects of treadmill exercise training (TET) for 8 weeks (13 m/min, 30 min/day, 5 days/week) on kidney injuries of type 2 diabetic male rats with obesity (Wistar fatty (fa/fa) rats: WFRs) at 36 weeks of age. TET significantly suppressed the levels of albuminuria and urinary liver-type fatty-acid-binding protein (L-FABP), tubulointerstitial fibrosis, inflammation, and oxidative stress in the kidneys of WFRs. In addition, TET mitigated excessive apoptosis and restored autophagy in the renal cortex, as well as suppressed the development of morphological abnormalities in the mitochondria of proximal tubular cells, which were also accompanied by the restoration of AMP-activated kinase (AMPK) activity and suppression of the mechanistic target of rapamycin complex 1 (mTORC1). In conclusion, TET ameliorates diabetes-induced kidney injury in type 2 diabetic fatty rats.

scholarly journals Epigenetic Modifiers as Potential Therapeutic Targets in Diabetic Kidney Disease

2020 ◽  
Vol 21 (11) ◽  
pp. 4113
Author(s):  
Julio M. Martinez-Moreno ◽  
Miguel Fontecha-Barriuso ◽  
Diego Martin-Sanchez ◽  
Juan Guerrero-Mauvecin ◽  
Elena Goma-Garces ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Epigenetic Regulation ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Sglt2 Inhibitors ◽  
Post Translational Modifications ◽  
Diabetic Kidney ◽  
Bet Inhibitor

Diabetic kidney disease is one of the fastest growing causes of death worldwide. Epigenetic regulators control gene expression and are potential therapeutic targets. There is functional interventional evidence for a role of DNA methylation and the histone post-translational modifications—histone methylation, acetylation and crotonylation—in the pathogenesis of kidney disease, including diabetic kidney disease. Readers of epigenetic marks, such as bromodomain and extra terminal (BET) proteins, are also therapeutic targets. Thus, the BD2 selective BET inhibitor apabetalone was the first epigenetic regulator to undergo phase-3 clinical trials in diabetic kidney disease with an endpoint of kidney function. The direct therapeutic modulation of epigenetic features is possible through pharmacological modulators of the specific enzymes involved and through the therapeutic use of the required substrates. Of further interest is the characterization of potential indirect effects of nephroprotective drugs on epigenetic regulation. Thus, SGLT2 inhibitors increase the circulating and tissue levels of β-hydroxybutyrate, a molecule that generates a specific histone modification, β-hydroxybutyrylation, which has been associated with the beneficial health effects of fasting. To what extent this impact on epigenetic regulation may underlie or contribute to the so-far unclear molecular mechanisms of cardio- and nephroprotection offered by SGLT2 inhibitors merits further in-depth studies.

scholarly journals Photobiomodulation of mineralisation in mesenchymal stem cells

2021 ◽  
Author(s):  
Sherif A. Mohamad ◽  
Michael R. Milward ◽  
Mohammed A. Hadis ◽  
Sarah A. Kuehne ◽  
Paul R. Cooper
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Respiratory Chain ◽  
Molecular Mechanisms ◽  
Therapeutic Potential ◽  
Positive Effects ◽  
Non Invasive ◽  
Light Delivery ◽  
Mineralisation Potential ◽  
Respiratory Chain Activity

AbstractMesenchymal stem cells (MSCs) and photobiomodulation (PBM) both offer significant therapeutic potential in regenerative medicine. MSCs have the ability to self-renew and differentiate; giving rise to multiple cellular and tissue lineages that are utilised in repair and regeneration of damaged tissues. PBM utilises light energy delivered at a range of wavelengths to promote wound healing. The positive effects of light on MSC proliferation are well documented; and recently, several studies have determined the outcomes of PBM on mineralised tissue differentiation in MSC populations. As PBM effects are biphasic, it is important to understand the underlying cellular regulatory mechanisms, as well as, provide accurate details of the irradiation conditions, to optimise and standardise outcomes. This review article focuses on the use of red, near-infra-red (R/NIR) and blue wavelengths to promote the mineralisation potential of MSCs; and also reports on the possible molecular mechanisms which underpin transduction of these effects. A variety of potential photon absorbers have been identified which are reported to mediate the signalling mechanisms, including respiratory chain enzymes, flavins, and cryptochromes. Studies report that R/NIR and blue light stimulate MSC differentiation by enhancing respiratory chain activity and increasing reactive oxygen species levels; however, currently, there are considerable variations between irradiation parameters reported. We conclude that due to its non-invasive properties, PBM may, following optimisation, provide an efficient therapeutic approach to clinically support MSC-mediated hard tissue repair. However, to optimise application, further studies are required to identify appropriate light delivery parameters, as well as elucidate the photo-signalling mechanisms involved.

scholarly journals Multi-scalar data integration links glomerular angiopoietin-tie signaling pathway activation with progression of diabetic kidney disease

2021 ◽  
Author(s):  
Jiahao Liu ◽  
Viji Nair ◽  
Yi-yang Zhao ◽  
Dong-yuan Chang ◽  
Felix Eichinger ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Diabetic Kidney Disease ◽  
Molecular Mechanisms ◽  
Receptor Expression ◽  
Diabetic Kidney ◽  
Scalar Data ◽  
Chinese Cohort ◽  
End Stage ◽  
Angiopoietin 2

Diabetes is the leading cause of chronic kidney disease. Prognostic biomarkers reflective of underlying molecular mechanisms are critically needed for effective management of diabetic kidney disease (DKD). In the Clinical Phenotyping and Resource Biobank study, an unbiased, machine learning approach identified a three-marker panel from plasma proteomics which, when added to standard clinical parameters, improved the prediction of outcome of end-stage kidney disease (ESKD) or 40% decline in baseline glomerular filtration rate (GFR) in a discovery DKD group (N=58) and was validated in an independent group (N=68) who also had kidney transcriptomic profiles available. Of the three markers, plasma angiopoietin 2 (ANGPT2) remained significantly associated with composite outcome in 210 Chinese Cohort Study of Chronic Kidney Disease participants with DKD. The glomerular transcriptional Angiopoietin/Tie (ANG-TIE) activation scores, derived from the expression of 154 literature-curated ANG-TIE signaling mediators, positively correlated with plasma ANGPT2 levels and outcome, explained by substantially higher TEK receptor expression in glomeruli and higher ANG-TIE activation scores in endothelial cells in DKD by single cell RNA sequencing. Our work suggests that activation of glomerular ANG-TIE signaling in the kidneys underlies the association of plasma ANGPT2 with disease progression, thereby providing potential targets to prevent DKD progression.

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