Mesenchymal stromal cells in renal ischemia/reperfusion injury

Vries, Dorottya K. de; Schaapherder, Alexander F.; Reinders, Marlies E.J.

doi:10.3389/fimmu.2012.00162

Cited by 28 publications

(32 citation statements)

References 114 publications

(117 reference statements)

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“…This property may help mitigating IRI (25, 26), rescuing marginal donor organs, reducing activation of innate immunity leading to progressive tissue fibrosis, and blunting ‘danger signals’ that could synergize with immune tolerance-inducing strategies ( Table 1 ).…”

Section: Introductionmentioning

confidence: 99%

Mesenchymal stromal (stem) cells to improve solid organ transplant outcome

Pileggi

Xu²,

Tan

et al. 2013

Current Opinion in Organ Transplantation

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Section: Introductionmentioning

confidence: 99%

Mesenchymal stromal (stem) cells to improve solid organ transplant outcome

Pileggi

Xu²,

Tan

et al. 2013

Current Opinion in Organ Transplantation

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“…Renal I/R injury in the early transplant period has been associated with acute rejection, delayed graft function, and late allograft failure (6) Mesenchymal stem cells of all bone marrow derived cells, hold special promise in attenuating kidney injury, since nephrons are largely of mesenchymal origin and stromal cells are of crucial importance for signaling leading to differentiation of both nephrons and collecting ducts (4).…”

Section: Discussionmentioning

confidence: 99%

“…Stem cells are pleuripotential cells with the ability to initiate repair mechanisms improving organ protection and repair (4). Mesenchymal stem cells (MSCs) are undifferentiated adult cells that can be isolated from a variety of tissues but primarily bone marrow stroma.…”

Section: Introductionmentioning

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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“…MSC therapy has been reported to improve outcomes in animal models of acute lung I/R injury [28][29][30] and renal I/R injury. 31 However, the relevance of these rodent studies to the clinical use of hAMSC remains to be determined. Employing larger animal models may provide more clinically relevant data.…”

mentioning

confidence: 99%

Human amniotic mesenchymal stem cells alleviate lung injury induced by ischemia and reperfusion after cardiopulmonary bypass in dogs

Qiang

Liang

2016

Laboratory Investigation

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Transplantation of mesenchymal stem cells may inhibit pathological immune processes contributing to ischemia/ reperfusion (I/R) injury. This study aimed to assess the capacity of human amniotic MSC (hAMSCs) to ameliorate I/R injury in a dog model of cardiopulmonary bypass (CPB). Dissociated hAMSCs were cultured ex vivo, and their immunophenotypes were assessed by flow cytometry and immunohistochemistry. A dog model of CPB was established by surgical blockage of the aorta for 1 h. Dogs either underwent mock surgery (Sham group), CPB (model group), or CPB, followed by femoral injection of 2 × 10 7 hAMSCs (n = 6). Anti-human nuclei staining revealed hAMSCs in the lungs 3 h after surgery. Oxygen index (OI) and respiratory index (RI) of arterial blood were measured using a biochemical analyzer. Venous blood TNF-α, IL-8, MMP-9, and IL-10 concentrations were measured by ELISA. Pathological changes in the lung were assessed by light microscopy. Third-generation-cultured hAMSCs expressed high levels of CD29, CD44, CD49D, CD73, and CD166 levels, but low CD34 or CD45 amounts and their cytoplasm contained Vimentin. In CPB model animals, OI was elevated and RI reduced; TNF-α, IL-8, and MMP-9 levels were elevated, and IL-10 levels reduced within 3h (Po0.05), but hAMSC transplantation significantly ameliorated these changes (Po0.05). Pathological changes observed in the hAMSC group were significantly less severe than those in the CPB group. In conclusion, hAMSC transplantation can downregulate proinflammatory factors and reduce MMP-9 levels, whereas upregulating the anti-inflammatory molecule IL-10, thus reducing I/R lung injury in a dog model of CPB.

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Mesenchymal stromal cells in renal ischemia/reperfusion injury

Cited by 28 publications

References 114 publications

Mesenchymal stromal (stem) cells to improve solid organ transplant outcome

Mesenchymal stromal (stem) cells to improve solid organ transplant outcome

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

Human amniotic mesenchymal stem cells alleviate lung injury induced by ischemia and reperfusion after cardiopulmonary bypass in dogs

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