scholarly journals Effect of Everolimus versus Bone Marrow-Derived Stem Cells on Glomerular Injury in a Rat Model of Glomerulonephritis: A Preventive, Predictive and Personalized Implication

2021 ◽  
Vol 23 (1) ◽  
pp. 344
Author(s):  
Mohamed M. Zedan ◽  
Ahmed K. Mansour ◽  
Ashraf A. Bakr ◽  
Mohamed A. Sobh ◽  
Hesam Khodadadi ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Adverse Effects ◽  
Rat Model ◽  
Inflammatory Responses ◽  
Early Stage ◽  
Control Group ◽  
Glomerular Mesangial Cells ◽  
Glomerular Injury ◽  
Endothelial Repair

Glomerular endothelial injury and effectiveness of glomerular endothelial repair play a crucial role in the progression of glomerulonephritis. Although the potent immune suppressive everolimus is increasingly used in renal transplant patients, adverse effects of its chronic use have been reported clinically in human glomerulonephritis and experimental renal disease. Recent studies suggest that progenitor stem cells could enhance glomerular endothelial repair with minimal adverse effects. Increasing evidence supports the notion that stem cell therapy and regenerative medicine can be effectively used in pathological conditions within the predictive, preventive and personalized medicine (PPPM) paradigm. In this study, using an experimental model of glomerulonephritis, we tested whether bone marrow-derived stem cells (BMDSCs) could provide better effect over everolimus in attenuating glomerular injury and improving the repair process in a rat model of glomerulonephritis. Anti-Thy1 glomerulonephritis was induced in male Sprague Dawley rats by injection of an antibody against Thy1, which is mainly expressed on glomerular mesangial cells. Additional groups of rats were treated with the immunosuppressant everolimus daily after the injection of anti-Thy1 or injected with single bolus dose of BMDSCs after one week of injection of anti-Thy1 (n = 6–8). Nine days after injection of anti-Thy1, glomerular albumin permeability and albuminuria were significantly increased when compared to control group (p < 0.05). Compared to BMDSCs, everolimus was significantly effective in attenuating glomerular injury, nephrinuria and podocalyxin excretion levels as well as in reducing inflammatory responses and apoptosis. Our findings suggest that bolus injection of BMDSCs fails to improve glomerular injury whereas everolimus slows the progression of glomerular injury in Anti-Thy-1 induced glomerulonephritis. Thus, everolimus could be used at the early stage of glomerulonephritis, suggesting potential implications of PPPM in the treatment of progressive renal injury.

Abstract 433: Renal Effects of Everolimus Versus Bone Marrow-derived Stem Cells in Rat Model of Glomerulonephritis

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Ahmed A Elmarakby ◽  
Chelsey Pye ◽  
Babak Baban ◽  
Mohamed M Zedan ◽  
Ashraf Bakr
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Barrier Function ◽  
Mesangial Cells ◽  
Endothelial Barrier ◽  
Control Group ◽  
Glomerular Mesangial Cells ◽  
Glomerular Injury ◽  
Endothelial Barrier Function ◽  
Endothelial Repair

The progression of renal disease is mainly influenced by degree of glomerular endothelial injury and effectiveness of glomerular endothelial repair. Considerable research efforts have recently been undertaken to examine glomerular endothelial repair by progenitor cells. We hypothesize that bone marrow-derived stem cells (BMDSCs) ameliorate experimental glomerulonephritis by restoring glomerular endothelial barrier function through improving the repair process. Anti-Thy1-glomerulonephritis was induced in Sprague Dawley rats by a single injection of an antibody against Thy1, which is mainly expressed on glomerular mesangial cells. Rats were then treated with the immunosuppressant everolimus (EV) daily or injected with isolated BMDSCs after one week of injection of anti-Thy1. After nine days of Injection of anti-Thy1, glomerular albumin permeability and albuminuria were significantly increased when compared to control group (P< 0.05). EV was superior than BMDSCs in attenuating the increase in glomerular albumin permeability and albuminuria in anti-Thy1 injected rats. However, only EV treatment significantly reduced the markers of glomerular injury, nephrinuria and podocalyxin excretion levels in anti-Thy1 injected rats (nephrinuria was 0.4± 0.1 vs. 0.8± 0.02 mg/day and podocalyxin excretion was 7± 1 vs. 11± 1 μg/day in EV treated vs. untreated anti-Thy1 injected rats, P< 0.05). Anti-Thy1 injected rats also showed hypercellular glomeruli with loss of Bowman space and variable number of lymphocyte and EV treatment partially restored these pathophysiological changes whereas BMDSCs had no significant effect. EV treatment also reduced number of renal CD3+ and macrophage and lowered IL-17 and caspase 3 levels in the anti-Thy1 injected rat kidneys. These data suggest that EV early treatment preserve glomerular endothelial barrier function in Anti-Thy1-induced glomerulonephritis via anti-apoptotic and anti-inflammatory mechanisms.

scholarly journals Ethanolic Extract of Centella asiatica Treatment in the Early Stage of Hyperglycemia Condition Inhibits Glomerular Injury and Vascular Remodeling in Diabetic Rat Model

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Wiwit A. W. Setyaningsih ◽  
Nur Arfian ◽  
Akbar S. Fitriawan ◽  
Ratih Yuniartha ◽  
Dwi C. R. Sari
Keyword(s):  
Diabetes Mellitus ◽  
Vascular Injury ◽  
Rat Model ◽  
Vascular Remodeling ◽  
Kidney Diseases ◽  
Early Stage ◽  
Vascular Dysfunction ◽  
Centella Asiatica ◽  
Control Group ◽  
Glomerular Injury

Background. Diabetes mellitus (DM) is marked by oxidative stress, inflammation, and vascular dysfunction that caused diabetic nephropathy that resulted in end-stage renal disease (ESRD). Vascular dysfunction is characterized by an imbalance in vasoconstrictor and vasodilator agents which underlies the mechanism of vascular injury in DM. Additionally, diminished podocytes correlate with the severity of kidney injury. Podocyturia often precedes proteinuria in several kidney diseases, including diabetic kidney disease. Centella asiatica (CeA) is known as an anti-inflammatory and antioxidant and has neuroprotective effects. This research aimed to investigate the potential effect of CeA to inhibit glomerular injury and vascular remodeling in DM. Methods. The DM rat model was induced through intraperitoneal injection of streptozotocin 60 mg/kg body weight (BW), and then rats were divided into 1-month DM (DM1, n = 5), 2-month DM (DM2, n = 5), early DM concurrent with CeA treatment for 2 months (DMC2, n = 5), and 1-month DM treated with CeA for 1-month (DM1C1, n = 5). The CeA (400 mg/kg BW) was given daily via oral gavage. The control group (Control, n = 5) was maintained for 2 months. Finally, rats were euthanized and kidneys were harvested to assess vascular remodeling using Sirius Red staining and the mRNA expression of superoxide dismutase, podocytes marker, ACE2, eNOS, and ppET-1 using RT-PCR. Results. The DM groups demonstrated significant elevation of glucose level, glomerulosclerosis, and proteinuria. A significant reduction of SOD1 and SOD3 promotes the downregulation of nephrin and upregulation of TRPC6 mRNA expressions in rat glomerular kidney. Besides, this condition enhanced ppET-1 and inhibited eNOS and ACE2 mRNA expressions that lead to the development of vascular remodeling marked by an increase of wall thickness, and lumen wall area ratio (LWAR). Treatment of CeA, especially the DMC2 group, attenuated glomerular injury and showed the reversal of induced conditions. Conclusions. Centella asiatica treatment at the early stage of diabetes mellitus ameliorates glomerulosclerosis and vascular injury via increasing antioxidant enzymes.

scholarly journals Bone-Marrow Stem Cells and Acellular Human Amniotic Membrane in a Rat Model of Heart Failure

Life ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 958
Author(s):  
Gustavo Gavazzoni Blume ◽  
Paulo André Bispo Machado-Junior ◽  
Rossana Baggio Simeoni ◽  
Giovana Paludo Bertinato ◽  
Murilo Sgarbossa Tonial ◽  
...  
Keyword(s):  
Heart Failure ◽  
Stem Cells ◽  
Bone Marrow ◽  
Amniotic Membrane ◽  
Rat Model ◽  
Connexin 43 ◽  
Left Ventricular ◽  
Bone Marrow Stem Cells ◽  
Control Group ◽  
Human Amniotic Membrane

Myocardial infarction (MI) remains the leading cause of cardiovascular death worldwide and a major cause of heart failure. Recent studies have suggested that cell-based therapies with bone marrow stem cells (BMSC) and human amniotic membrane (hAM) would recover the ventricular function after MI; however, the mechanisms underlying these effects are still controversial. Herein, we aimed to compare the effects of BMSC and hAM in a rat model of heart failure. MI was induced through coronary occlusion, and animals with an ejection fraction (EF) < 50% were included and randomized into three groups: control, BMSC, and hAM. The BMSC and hAM groups were implanted on the anterior ventricular wall seven days after MI, and a new echocardiographic analysis was performed on the 30th day, followed by euthanasia. The echocardiographic results after 30 days showed significant improvements on EF and left-ventricular end-sistolic and end-diastolic volumes in both BMSC and hAM groups, without significant benefits in the control group. New blood vessels, desmine-positive cells and connexin-43 expression were also elevated in both BMSC and hAM groups. These results suggest a recovery of global cardiac function with the therapeutic use of both BMSC and hAM, associated with angiogenesis and cardiomyocyte regeneration after 30 days.

Bone marrow mesenchymal stem cells can improve the motor function of a Huntington's disease rat model

2011 ◽  
Vol 33 (3) ◽  
pp. 331-337 ◽  
Author(s):  
Yufeng Jiang ◽  
Hailong Lv ◽  
Shanshan Huang ◽  
Huiping Tan ◽  
Yinong Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Motor Function ◽  
Rat Model ◽  
Marrow Mesenchymal Stem Cells

Transplantation of Bone Marrow Mesenchymal Stem Cells (BMSCs) Overexpressing Circular Zinc Finger Protein 609 Alleviates Diabetic Retinopathy

2021 ◽  
Vol 11 (12) ◽  
pp. 2497-2501
Author(s):  
Sheng Chen ◽  
Meiwen Tian ◽  
Shenwen Liu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Diabetic Retinopathy ◽  
Rat Model ◽  
Zinc Finger Protein ◽  
Retinal Thickness ◽  
Vitreous Body ◽  
Macular Volume ◽  
Marrow Mesenchymal Stem Cells

Diabetic retinopathy (DR) is a chronic complications and its pathogenesis remains unclear. This study aims to elucidate the underlying mechanism by how bone marrow mesenchymal stem cells (BMSCs) affects DR development in a rat model. A rat model of DR was established and injected with BMSCs overexpressing Cir-ZNF609 and shRNA Cir-ZNF609 to vitreous body followed by analysis of the retinal vascular permeability and macular retinal layers thickness, and the levels of HIF-1α, ICAM-1 and VEGF in rat retina by ELISA and immunohistochemistry. Injection of BMSCs overexpressing Cir-ZNF609 resulted in decreased HIF-1α ICAM-1 and VEGF expression, amelioration of retinal ganglion choriocapillaris injury and reducing ganglion cells. Twelve weeks after treatment, neovascularization took place and fibroblasts appeared with some nucleus disappearing and pigment taking off. Besides, permeability also elevated in the presence of overexpressing Cir-ZNF609 and penetration rate for Evans blue (16.36+3.25, 15.45±3.46 μg/g) was lower than healthy rats (28.66±2.08, 32.24±4.36 μg/g) and controls (26.93±3.03, 33.49±5.02 μg/g) (p < 0.01). Moreover, upregulation of Cir-ZNF609 decreased retinal thickness and macular volume in DR rats (p < 0.05). In conclusion, intravitreal injection of mouse BMSCs overexpressing Cir-ZNF609 alleviates retinal injury and decreases retinal thickness and macular volume, and enhances neovascularization. These evidence provides a novel insight into gene therapy for DR.

Abstract 239: Stem Cell Therapy Improves Critical Limb Ischemia

2012 ◽  
Vol 32 (suppl_1) ◽  
Author(s):  
Alaa Marzouk
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Embryonic Stem ◽  
Limb Ischemia ◽  
Control Group ◽  
Chronic Limb Ischemia

Introduction: The journey from single cell to complex being is attributable to stem cells role. Adult stem cells originate during ontogeny & persist in specialized niches within organs. Asymmetric division of each stem cell during differentiation produces : one daughter stem cell & one daughter transit amplifying/intermediate cell having migratory properties. Forced migration of hematopoietic stem/progenitor cells (HSPC) from bone marrow into peripheral blood is called mobilization. Accumulating evidence suggests that attenuation of the chemokine stromal derived factor-1(SDF-1)-CXCR4 axis that plays a pivotal role in retention of HSPC in bone marrow (BM) results in the release of these cells from the BM into peripheral blood. Recently, adult cells have been genetically reprogrammed to an embryonic stem cell like state. Induced pluripotent stem cells (IPSCs) were similar to human embryonic stem cells in morphology, proliferative capacity, expression of cell surface antigens, & gene expression. Treatment of ischemic vascular disease of lower limbs remains a significant challenge. Unfortunately, if medical & surgical salvage procedures fail, amputation is an unavoidable result for those patients. Aim of Work: (Hypothesis) To assess the application of implantation of autologous stem/progenitor cell in the treatment of chronic limb ischemia & to evaluate the safety, efficacy & feasibility of this novel therapeutic approach. Methods: A total of 24 patients with chronic limb ischemia not eligible for arterial reconstruction or endovascular procedures were enrolled & randomized (1:1) to either the implanted group or the control group. Control group: Conventional medical therapy in the form of anti platelet therapy & vasodilators. Implanted group: Subcutaneous injection of 300μ g/day of recombinant human granulocyte colony stimulating factor (G-CSF) for 5 days to mobilize stem/progenitor cells from BM. Total leucocytic count is measured daily to follow up successful mobilization of bone marrow mononuclear cells (BMMNCs). Stem cell Harvesting After 5 days peripheral blood mononuclear cells (PBMNCs) were harvested using a cell separator. Samples from apheresis products are subjected to TLC measurement & immunophenotypic characterization of CD34+ cells by flow cytometry. The collected PBMNCs were implanted by multiple intramuscular injections into ischemic limbs. Results: There was significant increase in pain free walking distance & ankle/brachial index (ABI) & significant decreased rest pain. Effectiveness was documented by : reduced number of amputation, increase ABI & improvement of the quality of life in therapeutic group compared to control group. Conclusion: The novel therapeutic approach of PBMNCs implantation in patients with chronic limb ischemia is safe, feasible & effective in decreasing co-morbidity & rate of amputation. Safety was manifested by absence of complications during G-CSF therapy or during harvesting & injection of the stem cells. Recommendations: 1- Future studies on larger number of patients & longer follow up. 2- Controlled studies using different methods & different cell population (PBMNCs, BMMNCs or MSCs) to compare the outcome of each. 3-Studing the role of endothelial progenitor cell dysfunction in different ischemic diseases to develop successful gene therapy.

Bone Marrow Mesenchymal Stem Cells (BMSCs) Transplantation Ameliorates Joint Severity and Inflammation in Rats with Arthritis

2022 ◽  
Vol 12 (5) ◽  
pp. 1028-1033
Author(s):  
Liangbang Wu ◽  
Zhenhai Hou ◽  
Longbao Zheng ◽  
Zenghui Gu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Rat Model ◽  
Inflammatory Cells ◽  
Type Ii Collagen ◽  
Rankl Expression ◽  
Positive Expression ◽  
Marrow Mesenchymal Stem Cells ◽  
Bovine Type

This study analyzed the action of Bone marrow mesenchymal stem cells (BMSCs) transplantation on arthritis rat model. Arthritis rat model was established using bovine type II collagen and CFA. BMSCs phenotype was assessed by flow cytometry and pathological changes was analyzed by H&E staining along with analysis of joint severity by AI score, inflammation by ELISA as well as level of NPY, MMP-2, and MMP-9. The form of passaged BMSCs was spindle shaped with positive expression of CD29 and CD44. The structure of articular cavity in arthritis rats was disordered with infiltration of inflammatory cells which were ameliorated by BMSCs transplantation. In addition, BMSCs treatment also significantly reduced AI value, the level of VEGF, IL-17 and TNF-α as well as decreased RANK/RANKL expression and increased OPG level. In conclusion, BMSCs transplantation ameliorates inflammation and severity in arthritis rats possibly through regulation of RANK/OPG, indicating that it might be used for the treatment of arthritis patients.

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