应用动物模型探索肾脏疾病作用机制和潜在治疗靶点

包寅武,; Bao, Yinwu; 袁圆,; 陈江华,; 林伟强,; Yuan, Yuan; Chen, Jianghua; Lin, Weiqiang

doi:10.24272/j.issn.2095-8137.2017.055

Cited by 82 publications

(27 citation statements)

References 197 publications

(214 reference statements)

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“…Since AKI is a life-threatening syndrome, we selected a lethal AKI model to confirm the function of ASC-exosomes in extremely harsh conditions. Cisplatin induces AKI in both humans and experimental animals, including rats and mice [ 46 , 47 ]. AKI was induced by intraperitoneal (IP) administration of 10 mg/kg cisplatin in Sprague-Dawley (SD) rats.…”

Section: Resultsmentioning

confidence: 99%

Reproducible Large-Scale Isolation of Exosomes from Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells and Their Application in Acute Kidney Injury

Lee¹,

Ha²,

Go³

et al. 2020

IJMS

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Acute kidney injury (AKI) is a fatal medical episode caused by sudden kidney damage or failure, leading to the death of patients within a few hours or days. Previous studies demonstrated that exosomes derived from various mesenchymal stem/stromal cells (MSC-exosomes) have positive effects on renal injuries in multiple experimental animal models of kidney diseases including AKI. However, the mass production of exosomes is a challenge not only in preclinical studies with large animals but also for successful clinical applications. In this respect, tangential flow filtration (TFF) is suitable for good manufacturing practice (GMP)-compliant large-scale production of high-quality exosomes. Until now, no studies have been reported on the use of TFF, but rather ultracentrifugation has been almost exclusively used, to isolate exosomes for AKI therapeutic application in preclinical studies. Here, we demonstrated the reproducible large-scale production of exosomes derived from adipose tissue-derived MSC (ASC-exosomes) using TFF and the lifesaving effect of the ASC-exosomes in a lethal model of cisplatin-induced rat AKI. Our results suggest the possibility of large-scale stable production of ASC-exosomes without loss of function and their successful application in life-threatening diseases.

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Section: Resultsmentioning

confidence: 99%

Reproducible Large-Scale Isolation of Exosomes from Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells and Their Application in Acute Kidney Injury

Lee¹,

Ha²,

Go³

et al. 2020

IJMS

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“…Most of the studies (n = 79) used animal models, including among others currently proposed AKI models (IR renal injury, including SWL; injection of drugs, toxins, or endogenous toxins; ureteral obstruction; CIN; trauma such as burn; etc.) [10][11][12][13][14][15][16] and variable definitions of AKI in line with the situation observed in human studies [2]. Only four human studies were detected: two preclinical studies utilizing human tissue [24,38] and two clinical trials [17,39].…”

Section: Resultsmentioning

confidence: 91%

“…Currently proposed AKI models include, among others: IR renal injury, including shock wave lithotripsy (SWL); injection of drugs, toxins, or endogenous toxins; ureteral obstruction, contrast-induced nephropathy (CIN); trauma such as burn; etc. [10][11][12][13][14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Current Concepts on the Reno-Protective Effects of Phosphodiesterase 5 Inhibitors in Acute Kidney Injury: Systematic Search and Review

Georgiadis

Zisis

Docea

et al. 2020

JCM

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Acute kidney injury (AKI) is associated with increased morbidity, prolonged hospitalization, and mortality, especially in high risk patients. Phosphodiesterase 5 inhibitors (PDE5Is), currently available as first-line therapy of erectile dysfunction in humans, have shown a beneficial potential of reno-protection through various reno-protective mechanisms. The aim of this work is to provide a comprehensive overview of the available literature on the reno-protective properties of PDE5Is in the various forms of AKI. Medline was systematically searched from 1946 to November 2019 to detect all relevant animal and human studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. In total, 83 studies were included for qualitative synthesis. Sildenafil is the most widely investigated compound (42 studies), followed by tadalafil (20 studies), icariin (10 studies), vardenafil (7 studies), zaprinast (4 studies), and udenafil (2 studies). Even though data are limited, especially in humans with inconclusive or negative results of only two clinically relevant studies available at present, the results of animal studies are promising. The reno-protective action of PDE5Is was evident in the vast majority of studies, independently of the AKI type and the agent applied. PDE5Is appear to improve the renal functional/histopathological alternations of AKI through various mechanisms, mainly by affecting regional hemodynamics, cell expression, and mitochondrial response to oxidative stress and inflammation.

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“…Additionally, in numerous previous studies, the confirmation of CKD-induced impaired kidney function was missing (42) making comparison with published experiments on behavioral outcomes of CKD severity very difficult. Furthermore, there are several animal models of CKD differing in signs and symptoms (52,53). Thus, the development of neurobehavioral disorders related to CKD may depend on the model used, which should be considered in future studies.…”

Section: Discussionmentioning

confidence: 99%