Adipose-Derived Mesenchymal Stem Cells Transplantation Alleviates Renal Injury in Streptozotocin-Induced Diabetic Nephropathy

Ni, Wenjie; Fang, Yan; Xie, Ling; Lü, Xue; Shan, Wei; Zeng, Ruixia; Liu, Jiansheng; Liu, Xueyuan

doi:10.1369/0022155415599039

Cited by 37 publications

(26 citation statements)

References 43 publications

(51 reference statements)

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“…caspase-3, cleaved caspase-3 and Bax and increasing the levels of anti-apoptotic marker, Bcl-2 in the heart of diabetic rats. MSCs and adipose-derived MSCs transplantation was reported to reduce STZ-induced renal injury and renal tissue cell apoptosis 64 , and to decrease the apoptosis rate and the expression of Bax and elevated Bcl-2 in kidney in diabetic rats 65 . Umbilical cord blood –MSCs, have also been shown to improve cardiac structure and function in a transgenic mouse of dilated cardiomyopathy mouse, an effect that was associated with reductions in cellular apoptosis, inflammation, hypertrophy and myocardial fibrosis and up-regulation of Bcl 2 21 .…”

Section: Discussionmentioning

confidence: 99%

Mechanistic insights into the augmented effect of bone marrow mesenchymal stem cells and thiazolidinediones in streptozotocin-nicotinamide induced diabetic rats

Hamza

Fikry

Abdallah

et al. 2018

Sci Rep

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This study was designed to assess whether the protective effects of bone marrow-derived mesenchymal stem cells (MSCs) against diabetes could be enhanced by pioglitazone (PIO), a PPARγ agonist. Combined MSCs and PIO treatments markedly improved fasting blood glucose, body weight, lipid profile levels, insulin level, insulin resistance, β cell function. Those protective effects also attenuated both pancreatic lesions and fibrosis in diabetic rats and decreased the depletion of pancreatic mediators of glycemic and lipid metabolism including peroxisome proliferator-activated receptor alpha (PPARα), PGC-1α, GLP-1 and IRS-2. Cardiac biogenesis of diabetic groups was also improved with MSCs and/or PIO treatments as reflected by the enhanced up-regulation of the expressions of cardiac IRS1, Glucose transporter 4, PGC-1, PPARα and CPT-1 genes and the down-regulated expression of lipogenic gene SREBP. The combination of MSCs and PIO also potentiated the decrease of abnormal myocardial pathological lesions in diabetic rats. Similarly, the inhibitory effects of MSCs on diabetic cardiac fibrosis and on the up regulations of TGF-β, collagen I and III gene expressions were partial but additive when combined with PIO. Therefore, combined therapy with PIO and BMCs transplantation could further potentiate the protective benefit of MSCs against diabetes and cardiac damage compared to MSCs monotherapy.

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Section: Discussionmentioning

confidence: 99%

Mechanistic insights into the augmented effect of bone marrow mesenchymal stem cells and thiazolidinediones in streptozotocin-nicotinamide induced diabetic rats

Hamza

Fikry

Abdallah

et al. 2018

Sci Rep

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show abstract

“…In addition, the anti-brosis effect of BM-MSCs was enhanced by miRNA-124a, which was potentially related to the suppression of cav-1 and β-catenin activation. ADSCs alleviated DN renal injury by activating klotho and inhibiting Wnt/β-catenin signaling pathway, and klotho gene knockout decreased the expressions of apoptosis-regulated proteins and members of the Wnt/β-catenin signaling pathway [48].…”

Section: Regenerationmentioning

confidence: 97%

Mesenchymal Stem Cells Transplantation in Diabetic Kidney Diseases: A Systematic Review and Meta-analysis

Lin¹,

Yang²,

Chen³

et al. 2020

Preprint

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Background: Mesenchymal stem cells (MSCs) therapy shows great promise for diabetic kidney diseases (DKD) patients. Researches have been carried out on this topic in recent years. The main thrust of this paper is to evaluate the therapeutic effects of MSCs on DKD by a meta-analysis and systematically review the mechanism therein. Method: An electronic search of PubMed and U.S National Library of Medicine (NLM) was performed for all articles about the MSCs therapy for DKD without species limitation up to January, 2020. Data were pooled for analysis with Stata SE 12. Result: MSCs-treated group showed great significant hypoglycemic effect at 1 week, 2 weeks, 3 weeks, 1 month, 2 months, 3 months and 6 months. Total hypoglycemic effect was analyzed (SMD=-1.954, 95%CI: -2.389 to -1.519, I²= 85.1%, p＜0.001). Total effects on serum creatinine (SCr), blood urea nitrogen (BUN) were analyzed, suggesting MSCs decreased the SCr and BUN and had an effect on amelioration of impaired renal function (SCr: SMD= -4.838, 95%CI: -6.789 to -2.887, I²= 90.8%, p＜0.001; BUN: SMD= -4.912, 95%CI: -6.402 to -3.422, I²= 89.3 %, p＜0.001). Creatinine clearance rate (CCr) was found decreased in the MSCs-treated group at 2 months. MSCs therapy decreased the excretion of urinary albumin. The fibrosis indicators were detected, and the result showed that transforming growth factor-β, Collagen-I, fibronectin and α-smooth muscle actin were seen decreased significantly in the MSCs-treated group. Conclusion: MSCs might improve animal body weight, glycemic control and pancreas islets function to secrete insulin, and reduced the SCr, BUN, CCr, urinary protein and renal hypertrophy. MSCs can reduce the expression of inflammatory mediators and alleviate renal fibrosis. MSCs therapy is a potential treatment for DKD.

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“…Klotho-modified MSCs have superior therapeutic effects in AKI that are associated with the inhibition of Wnt/β-catenin signaling [ 119 ]. Further studies have also shown that adipose-derived MSC transplantation promotes Klotho expression in diabetic nephropathy, blocks Wnt/β-catenin signaling, and attenuates renal injury [ 120 ]. These results suggest that Klotho and stem cells mutually reinforce each other.…”

Section: Therapeutic Potentials Of Targeting Wnt Signalingmentioning

confidence: 99%

Wnt signaling in kidney: the initiator or terminator?

et al. 2020

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The kidney is a key organ in the human body that excretes toxins and sustains the water–electrolyte balance. During embryonic development and disease progression, the kidney undergoes enormous changes in macrostructure, accompanied by a variety of microstructural histological changes, such as glomerular formation and sclerosis, tubule elongation and atrophy, interstitial establishment, and fibrosis progression. All of these rely on the frequent occurrence of cell death and growth. Notably, to overcome disease, some cells regenerate through self-repair or progenitor cell differentiation. However, the signaling mechanisms underlying kidney development and regeneration have not been elucidated. Recently, Wnt signaling has been noted to play an important role. Although it is a well-known developmental signal, the role of Wnt signaling in kidney development and regeneration is not well recognized. In this review, we review the role of Wnt signaling in kidney embryonic development, tissue repair, cell division, and progenitor cell differentiation after injury. Moreover, we briefly highlight advances in our understanding of the pathogenic mechanisms of Wnt signaling in mediating cellular senescence in kidney parenchymal and stem cells, an irreversible arrest of cell proliferation blocking tissue repair and regeneration. We also highlight the therapeutic targets of Wnt signaling in kidney diseases and provide important clues for clinical strategies.

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Adipose-Derived Mesenchymal Stem Cells Transplantation Alleviates Renal Injury in Streptozotocin-Induced Diabetic Nephropathy

Cited by 37 publications

References 43 publications

Mechanistic insights into the augmented effect of bone marrow mesenchymal stem cells and thiazolidinediones in streptozotocin-nicotinamide induced diabetic rats

Mechanistic insights into the augmented effect of bone marrow mesenchymal stem cells and thiazolidinediones in streptozotocin-nicotinamide induced diabetic rats

Mesenchymal Stem Cells Transplantation in Diabetic Kidney Diseases: A Systematic Review and Meta-analysis

Wnt signaling in kidney: the initiator or terminator?

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