Mesenchymal Stromal Cells Do Not Protect Against Renal Ischaemia Reperfusion Injury in Either an In Vitro Human Model or an In Vivo Murine Model.

2014 ◽  
Vol 98 ◽  
pp. 349
Author(s):  
C. Clark ◽  
G. Gobe ◽  
S. McTaggart
2019 ◽  
Vol 858 ◽  
pp. 172489 ◽  
Author(s):  
Louis Higgins ◽  
Siripong Palee ◽  
Siriporn C. Chattipakorn ◽  
Nipon Chattipakorn

1996 ◽  
Vol 45 (S1) ◽  
pp. S27-S28 ◽  
Author(s):  
E. Masini ◽  
D. Salvemini ◽  
L. Mugnai ◽  
M. G. Bello ◽  
D. Bani ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Minghua Deng ◽  
Jingyuan Wang ◽  
Hao Wu ◽  
Menghao Wang ◽  
Ding Cao ◽  
...  

Background. Liver ischaemia-reperfusion injury (IRI) remains a problem in liver transplantation. Interleukin-4 (IL-4) has been found to reduce liver IRI, but the exact mechanism remains unclear. Methods. Donor livers were infused with recombinant IL-4 or normal saline during cold storage, and the hepatocellular apoptosis and the inflammatory response were detected. The effect of IL-4 treatment on Kupffer cells (KCs) polarization and expression of the STAT6-JMJD3 pathway was evaluated in vivo and in vitro. KCs in donor livers were depleted by clodronate liposome treatment or JMJD3 was inhibited by GSK-J4 before liver transplantation to determine whether the protective effect of IL-4 treatment was dependent on KCs. Results. IL-4 treatment decreased sALT and sAST levels and alleviated hepatocellular apoptosis and inflammation at 6 h after liver transplantation. IL-4 treatment induced KCs alternatively activated (M2) polarization in vitro and in vivo, and the expression of STAT6 and JMJD3 was increased. JMJD3 knockdown abolished KCs M2 polarization and reduced the antiapoptotic and anti-inflammatory effects induced by IL-4 treatment in vitro. In addition, the protection of IL-4 treatment against IRI induced by liver transplantation was significantly reduced after the depletion of KCs or the inhibition of JMJD3 in donor livers. Conclusions. IL-4 treatment-induced KCs M2 polarization was dependent on the STAT6-JMJD3 pathway and protected liver grafts from IRI after liver transplantation.


2017 ◽  
Vol 51 (2) ◽  
pp. e12400 ◽  
Author(s):  
Jia Wang ◽  
Fengzhen Wang ◽  
Zhuojun Wang ◽  
Shulin Li ◽  
Lu Chen ◽  
...  

1995 ◽  
Vol 89 (s33) ◽  
pp. 31P-31P
Author(s):  
N J Lane ◽  
M S Thorniley ◽  
S Manek ◽  
B J Fuller ◽  
C J Green

2019 ◽  
Author(s):  
Rachel Harwood ◽  
Joshua Bridge ◽  
Lorenzo Ressel ◽  
Lauren Scarfe ◽  
Jack Sharkey ◽  
...  

BackgroundRenal Ischaemia Reperfusion Injury (R-IRI) can cause Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD), resulting in significant morbidity and mortality. To understand the underlying mechanisms, reproducible small-animal models of AKI and CKD are needed. We describe how innovative technologies for measuring kidney function non-invasively in small rodents allow successful refinement of the R-IRI models, and offer the unique opportunity to monitor longitudinally in individual animals the transition from AKI to CKD.MethodsMale BALB/c mice underwent bilateral renal pedicle clamping (AKI) or unilateral renal pedicle clamping with delayed contralateral nephrectomy (CKD) under isoflurane anaesthetic. Transdermal GFR monitoring and multi-spectral optoacoustic tomography in combination with statistical analysis were used to identify and standardise variables within these models.ResultsPre-clamping anaesthetic time was one of the most important predictors of AKI severity after R-IRI. Standardising pre-clamping time resulted in a more predictably severe AKI model. In the CKD model, initial improvement in renal function was followed by significant progressive reduction in function between weeks 2 and 4. Performing contralateral nephrectomy on day 14 enabled the development of CKD in a survivable way.ConclusionsNon-invasive monitoring of global and individual renal function after R-IRI is feasible, reproducible and correlates well with classical markers of injury. This facilitates refinement of kidney injury models and enables the degree of injury seen in pre-clinical models to be translated to those seen in the clinical setting. Thus, future therapies can be tested in a clinically relevant, non-invasive manner.What is already knownThe severity of Renal Ischaemia Reperfusion injury (R-IRI) varies between animal strain, gender and age. Experimental variables including temperature and clamping time are usually tightly controlled but significant variability still exists. Classically, small rodent experiments depend on endpoint evaluation of serum and histological features of disease. However, new technologies including transdermal glomerular filtration rate (GFR) monitoring and Multispectral Optoacoustic Tomography (MSOT) may enable renal function to be accurately monitored longitudinally, enabling better refinement of these models.What this study addsThis study shows that transdermal GFR measurements have reliably enabled refinement of the R-IRI model by standardisation of the duration of isoflurane prior to commencing surgery. Individual kidney function can be assessed in-vivo after unilateral R-IRI using MSOT imaging. The excretion tmax of IRDye-800 reliably represents the relative function of the injured kidney, permitting longitudinal in-vivo assessment of differential kidney function.What impact this may have on practiceThis study demonstrates the utility of two minimally-invasive in-vivo methods of monitoring kidney function which have advantages over classical methods and potentially enable fewer animals to be used in future studies. The study demonstrates refinement of bilateral and unilateral R-IRI models which will also enable a reduction in the number of animals needed for experimentation.


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