Evaluation of the effect of autologous mesenchymal stem cell injection in a large‐animal model of bilateral kidney ischaemia reperfusion injury

Behr, L.; Hekmati, Mehrak; Lucchini, A; Houcinet, K.; Faussat, Anne-Marie; Borenstein, Nicolas; Nôël, Laure-Hélène; Lelièvre-Pégorier, Martine; Laborde, Kathleen

doi:10.1111/j.1365-2184.2009.00591.x

Cited by 47 publications

(35 citation statements)

References 56 publications

(133 reference statements)

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“…The results obtained in this study contradict those in another report that showed the non-therapeutic effects of MSC transplantation in an ovine model of renal injury (37). Considering other reports, the mechanism by which cUCB-MSCs contribute to ameliorating renal failure in the present study could be related to the MSC secretome or prevention of progressive pathology or transdifferentiation of MSCs (38,39).…”

Section: Detection Of Transplanted Mesenchymal Stem Cells In the Kidncontrasting

confidence: 57%

Mesenchymal Stem Cells Contribute to Improvement of Renal Function in a Canine Kidney Injury Model

Lee

Ryu

Seo

et al. 2017

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Section: Detection Of Transplanted Mesenchymal Stem Cells In the Kidncontrasting

confidence: 57%

Mesenchymal Stem Cells Contribute to Improvement of Renal Function in a Canine Kidney Injury Model

Lee

Ryu

Seo

et al. 2017

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“…In the cortex, MSCs were found in glomeruli and were rarely identified in the renal microvasculature. The MSC was not found in renal tubules (7).…”

Section: Discussionmentioning

confidence: 98%

“…Behr et al (2009) found that 60 min. bilateral ischemia induced mild renal injury with focal acute tubular necrosis; this pattern of lesions is closer to that observed in humans with ARF (7).…”

Section: Discussionmentioning

confidence: 99%

“…No significant differences was observed in serum creatinine in MSC treated dogs when compared with non treated dogs or change the course of renal IRI. Behr et al (2009) (7) found that in sheep model of IRI was followed by significant increase in plasma renin activity, creatinine/ BUN concentrations, and urinary sodium excretion, consequences of renal vasoconstriction, reduced glomerular filtration rate and tubular injury secondary to renal ischaemia. No significant difference in these parameters was observed after MSCs infusion during the 7-day period following our IRI.…”

Section: Discussionmentioning

confidence: 99%

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Mesenchymal Stem Cells Home to but do not Modulate Acute Renal Injury in a Canine Model

Gabr¹

2014

IJBSE

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Background: Acute kidney injury (ARI) is a common clinical event that occurs in 5-35% of all hospitalizedpatients and is associated with a two-to five fold increased mortality risk., with no significant improvement on pharmacologic therapy. The need for better treatment strategies for ARI called for cellular based strategies aiming to regenerate damaged tissues. Mesenchymal stem cells (MSCs) hold special promise in attenuating kidney injury, since nephrons are largely of mesenchymal origin. Objectives: The objective of this study is to evaluate the role of bone marrow derived (MSCs) in regeneration of post-ischemic acute renal injury in mongrel dogs. Material and Methods: Fifteen adult male mongrel dogs were used in this study. Animals were divided into: Group I, normal group (3 dogs); Group II, nine dogs subjected to ischemic/reperfusion injury (IRI) by clamping both renal pedicles for 60 minutes and not subjected to stem cell therapy which were further divided into: 6 dogs without sham injection, 3 sacrificed 3 days and 3 after 7 days after IRI and 3 dogs with sham injection sacrificed 7 days after IRI. and Group III (3 dogs) which underwent IRI and received systemic autologous MSC injection. This group underwent aspiration of 15-20 ml bone marrow from posterior iliac spine, mononuclear cell separation and MSC separation. MSCs were tagged by iron oxide and injected in a dose of 2million /kg systemically through the femoral vein. Evaluation of Therapeutic Effect: 1. Functional evaluation of renal functions using serum creatinine preoperative and 30 minutes, 1 day, 2days, 4days, 7days postoperative.2. Renal histology and injury scores: using H&E, PAS using morphometry. 3. Tracing of injected MSCs (homing) in renal tissues using Prussian blue staining . 4. Immunohistochemical evaluation of the apoptosis and proliferative capacity of MSCs using caspase3 and KI 67. Results: Bone marrow derived MSCs were found in the renal cortex and medulla, epithelial lining of the cortical tubules, glomeruli, the Bowman's space, in some peritubular capillaries and among the epithelial lining of the renal tubules of treated animals. However,MSCs did not undergo transdifferentiation to renal cells, There was no difference in the regeneration, apoptosis or proliferation between treated and nontreated animals. Conclusions: Injected MSCs homed to but did not affect regeneration of renal tissue after acute injury. Although MSCs did not prove to differentiate into renal tissue, they can be used as vehicles for cytokines or growth factors as they home to injured sites.

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“…CXCR4 gene transfer contributes to in vivo reendothelialization capacity of endothelial progenitor cells (28). However, some studies show that MSC could not exhibit reparative or paracrine protective properties (29). Confirmation of the exact effects of MSC on vascular injury is needed .…”

Section: Discussionmentioning

confidence: 99%

Protective Effects of Mesenchymal Stem Cells with Transient Overexpression of Hmgb1 on Balloon-Induced Carotid Artery Injury

2012

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The first two authors contributed equally to this study Mesenchymal stem cells (MSC) playa crucial role in endothelial repair after artery injury. The high mobility group box 1 (HMGBl) is a key modulator of the homing of MSC to impaired artery and endothelialization. This study was aimed to determine whether balloon-induced carotid artery injury could be improved by transplantation with MSC modified by HMGBI. MSC were infected by adenoviral serotype 5 encoding recombinant green fluorescent protein (GFP) gene and HMGBI (ad5GFP-HMGBl). The expression ofHMGBl, vascular endothelial growth factor (VEGF) and proliferating cell nuclear antigen (PCNA) was detected in MSC using Real-time PCR, Western blot and semi-quantitative immunohistochemical assays. In vivo, reendothelialization was examined in rats subjected to carotid artery injury. The homing of MSC was observed under fluorescence microscopy, and the levels of serum tumor necrosis factor-a (TNF-a) and C-reactive protein (CRP) was assessed by ELISA assay. As a result, compared with the MSC group, the expression of HMGBl, VEGF and PCNA was markedly increased, vascular reendothelialization was accelerated, and the levels of serum TNF-a and CRP were decreased in group ad5GFP and ad5GFP-HMGBl. Transplantation of MSC infected with adGFP-HMGBl strengthened the MSC effect. Taken together, modification ofHMGBl can enhance the protective effects ofMSC on balloon-induced carotid artery injury through up-regulation ofVEGF and PCNA expression and inhibition ofthe inflammatory response. HMGBI in MSC may represent a novel therapeutic target for the treatment of endothelial repair.

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Evaluation of the effect of autologous mesenchymal stem cell injection in a large‐animal model of bilateral kidney ischaemia reperfusion injury

Abstract: In this unique autologous large-animal model, MSCs did not exhibit reparative or paracrine protective properties.

Cited by 47 publications

References 56 publications

Mesenchymal Stem Cells Contribute to Improvement of Renal Function in a Canine Kidney Injury Model

Mesenchymal Stem Cells Contribute to Improvement of Renal Function in a Canine Kidney Injury Model

Mesenchymal Stem Cells Home to but do not Modulate Acute Renal Injury in a Canine Model

Protective Effects of Mesenchymal Stem Cells with Transient Overexpression of Hmgb1 on Balloon-Induced Carotid Artery Injury

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