scholarly journals Mesenchymal Stem Cell-Derived Exosomes Ameliorated Diabetic Nephropathy by Autophagy Induction through the mTOR Signaling Pathway

Cells ◽  
2018 ◽  
Vol 7 (12) ◽  
pp. 226 ◽  
Author(s):  
Nesrine Ebrahim ◽  
Inas Ahmed ◽  
Noha Hussien ◽  
Arigue Dessouky ◽  
Ayman Farid ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Renal Function ◽  
Diabetic Nephropathy ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Renal Tissue ◽  
Beclin 1 ◽  
Protective Mechanism ◽  
Defensive Role ◽  
Autophagy Induction

Background: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus and a common cause of end-stage renal disease. Autophagy has a defensive role against kidney damage caused by hyperglycemia. Mesenchymal stem cell (MSC)-derived exosomes are currently considered as a new promising therapy for chronic renal injury. However, the renal-protective mechanism of exosomes on DN is not completely understood. We examined the potential role of MSC-derived exosomes for enhancement of autophagy activity and their effect on DN. In our study, we used five groups of rats: control; DN; DN treated with exosomes; DN treated with 3-methyladenine (3-MA) and chloroquine (inhibitors of autophagy); and DN treated with 3-methyladenine (3-MA), chloroquine, and exosome groups. We assessed renal function, morphology, and fibrosis. Moreover, ratios of the autophagy markers mechanistic target of rapamycin (mTOR), Beclin-1, light chain-3 (LC3-II), and LC3-II/LC3-I were detected. Additionally, electron microscopy was used for detection of autophagosomes. Results: Exosomes markedly improved renal function and showed histological restoration of renal tissues, with significant increase of LC3 and Beclin-1, and significant decrease of mTOR and fibrotic marker expression in renal tissue. All previous effects were partially abolished by the autophagy inhibitors chloroquine and 3-MA. Conclusion: We conclude that autophagy induction by exosomes could attenuate DN in a rat model of streptozotocin-induced diabetes mellitus.

scholarly journals Mesenchymal Stem Cell-Derived Exosomes Ameliorated Diabetic Nephropathy by Autophagy Induction through mTOR Signaling Pathway

2018 ◽  
Author(s):  
Nesrine Ebrahim ◽  
Inas A. Ahmed ◽  
Noha I. Hussien ◽  
Arigue A. Dessouky ◽  
Ayman Samir Farid ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Renal Tissue ◽  
Beclin 1 ◽  
Protective Mechanism ◽  
Renal Functions ◽  
Defensive Role ◽  
Autophagy Induction ◽  
Stage Renal Disease ◽  
End Stage

Background: diabetic nephropathy (DN) is a serious complication of diabetes mellitus and a common cause for end stage renal disease. Autophagy has a defensive role against kidney damage caused by hyperglycemia. The mesenchymal stem cells (MSCs) derived exosomes are currently considered as a new promising therapy in chronic renal injury. However, the renal protective mechanism of exosomes on DN has not been completely understood. We examined the potential role of MSCs derived exosomes in enhancement of autophagy activity and its effect on DN. In our study we used five groups of rats; control, DN, DN treated with exosomes, DN treated with 3-methyladenine (3-MA) and chloroquine (inhibitors of autophagy) and DN treated with 3-methyladenine (3-MA) and chloroquine and exosomes groups. We assessed renal functions, morphology and fibrosis. Moreover, autophagy markers; mTOR, Beclin-1, light chain-3 (LC3-II), and LC3-II/LC3-I ratio were detected. Additionally, electron microscopy was used for detection of autophagosomes. Results: Exosomes markedly improved the renal functions and showed histological restoration of renal tissues with significant increase in LC3 and Beclin-1 besides the significant decrease in mTOR and fibrotic markers expression in renal tissue. All previous effects were partially abolished by the autophagy inhibitor, chloroquine and 3-MA. Conclusions: we conclude that autophagy induction by exosomes could attenuate DN in a rat model of streptozotocin-induced diabetes mellitus.

scholarly journals The structural and functional recovery of pancreatic β-cells in type 1 diabetes mellitus induced mesenchymal stem cell-conditioned medium

2016 ◽  
Vol 9 (5) ◽  
pp. 535-539 ◽  
Author(s):  
Widagdo Sri Nugroho ◽  
Dwi Liliek Kusindarta ◽  
Heru Susetya ◽  
Ida Fitriana ◽  
Guntari Titik Mulyani ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Type 1 Diabetes Mellitus ◽  
Functional Recovery ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Cell Conditioned Medium

Hyperoside ameliorates glomerulosclerosis in diabetic nephropathy by downregulating miR-21

2016 ◽  
Vol 94 (12) ◽  
pp. 1249-1256 ◽  
Author(s):  
Le Zhang ◽  
Siyi He ◽  
Fan Yang ◽  
Hua Yu ◽  
Wei Xie ◽  
...  
Keyword(s):  
Renal Function ◽  
Diabetic Nephropathy ◽  
Mesangial Cells ◽  
Periodic Acid ◽  
Protective Mechanism ◽  
Therapeutic Effects ◽  
Protein Levels ◽  
Tissue Inhibitors Of Metalloproteinase ◽  
Underlying Mechanisms

The purpose of this study was to investigate the therapeutic effects of hyperoside (Hyp) on glomerulosclerosis in diabetic nephropathy and its underlying mechanisms. Blood glucose, kidney mass, and renal function of mice were measured. Renal morphology was observed using hematoxylin and eosin, periodic acid – Schiff’s, and Masson’s trichrome stain. Fibronectin (FN) and collagen IV (COL IV) in kidney were determined by Western blot and immunohistochemical studies. Matrix metalloproteinases (MMP)-2 and -9 and tissue inhibitors of metalloproteinase (TIMP)-1 in renal tissues were detected on both the mRNA and protein levels. miRNA expression and artificial alterations by miRNA agomir transfection were evaluated to investigate the protective mechanism of Hyp in mesangial cells. Hyp effectively improved renal function and physiologic features of db/db mice. Hyp also ameliorated glomerulosclerosis by suppressing FN, COL IV, and TIMP-1 expressions and promoting MMP-9 and MMP-2 expressions. The change in MMP-9 mRNA expression was inconsistent with that in protein levels in kidney, indicating that there was a post-transcriptional regulation. Further exploration in vitro showed that miR-21 was downregulated by Hyp, increasing expression of its target, MMP-9. These results suggest that Hyp can ameliorate glomerulosclerosis in diabetic nephropathy by downregulating miR-21 to increase expression of its target, MMP-9.

Autologous Mesenchymal Stem Cell Transplant in Patients with Type 1 Diabetes Mellitus

2019 ◽  
Vol 17 (Suppl 1) ◽  
pp. 236-238 ◽  
Author(s):  
Olga Ulyanova ◽  
◽  
Manarbek Askarov ◽  
Larissa Kozina ◽  
Temirlan Karibekov ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 1 Diabetes ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Type 1 Diabetes Mellitus ◽  
Stem Cell Transplant ◽  
Cell Transplant

A randomised double-blind, placebo-controlled trial of allogeneic umbilical cord-derived mesenchymal stem cell for lupus nephritis

2017 ◽  
Vol 76 (8) ◽  
pp. 1436-1439 ◽  
Author(s):  
DanQi Deng ◽  
Peilian Zhang ◽  
Yun Guo ◽  
Teck Onn Lim
Keyword(s):  
Renal Function ◽  
Stem Cell ◽  
Lupus Nephritis ◽  
Mesenchymal Stem Cell ◽  
Umbilical Cord ◽  
Treatment Effect ◽  
Activity Index ◽  
Immunosuppressive Treatment ◽  
Similar Proportion ◽  
Human Umbilical Cord

ObjectiveWe evaluate the efficacy of human umbilical cord-derived mesenchymal stem cell (hUC-MSC) for the treatment of lupus nephritis (LN). Previous reports showed hUC-MSC could have dramatic treatment effect.MethodsEighteen patients with WHO class III or IV LN were randomly assigned to hUC-MSC (dose 2×108 cells) or placebo. All patients received standard immunosuppressive treatment, which consisted of intravenous methylprednisolone and cyclophosphamide, followed by maintenance oral prednisolone and mycophenolate mofetil.ResultsRemission occurred in 9 of 12 patients (75%) in the hUC-MSC group and 5 of 6 patients (83%) in the placebo group. Remission was defined as stabilisation or improvement in renal function, reduction in urinary red cells and protein. A similar proportion of patients on hUC-MSC and placebo achieved complete remission. Improvements in serum albumin, complement, renal function, Systemic Lupus Erythematosus Disease Activity Index and British Isles Lupus Assessment Group scores were similar in both groups. One patient on placebo had a stroke and another had ascites. One patient on hUC-MSC had leucopenia, pneumonia and subcutaneous abscess and another died of severe pneumonia. The trial was abandoned after 18 patients were enrolled when it had become obvious it would not demonstrate a positive treatment effect.ConclusionhUC-MSC has no apparent additional effect over and above standard immunosuppression.Trial registration numberNCT01539902; Results.

scholarly journals Concise Review: Mesenchymal Stem Cell Treatment of the Complications of Diabetes Mellitus

Stem Cells ◽  
2011 ◽  
Vol 29 (1) ◽  
pp. 5-10 ◽  
Author(s):  
Vladislav Volarevic ◽  
Nebojsa Arsenijevic ◽  
Miodrag L. Lukic ◽  
Miodrag Stojkovic
Keyword(s):  
Diabetes Mellitus ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Complications Of Diabetes ◽  
Concise Review ◽  
Stem Cell Treatment ◽  
Mesenchymal Stem Cell Treatment
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