scholarly journals Platelet-rich plasma enhanced MSCs repair for glycerin-induced acute kidney injury via AKT/Rab27 paracrine pathway

2020 ◽  
Author(s):  
Cheng Ji ◽  
Jiahui Zhang ◽  
Zixuan Zhou ◽  
Hui Shi ◽  
wanzhu Liu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Therapeutic Effect ◽  
Platelet Rich Plasma ◽  
Kidney Injury ◽  
Human Umbilical Cord ◽  
Renal Tubular Cells

Abstract Background: Acute kidney injury (AKI) was defined by rapid deterioration of renal function, as a common complication in hospitalized patients. Among the recent therapeutic options, mesenchymal stem cells (MSCs) were considered a promising therapeutic strategy for damaged tissues repair. Platelet rich plasma (PRP) regulates stromal cells to repair tissue damage through the release of growth factors. Here we proposed a possible therapeutic use of human umbilical cord mesenchymal stem cells stimulated by platelet-rich plasma (PRP-MSCs) in glycerin-induced acute kidney injury murine model.Methods: In vivo, we constructed glycerin-induced acute kidney injury rat models. On day 1 post injury, rat received a tail vein injection of 1×106 MSCs and 1×106 PRP-MSCs. All animals were sacrificed at Day 3 after glycerin injection. In vitro, NRK-52E cells were damaged by 20% glycerol for 12 hours, after that NRK-52E incubated with MSCs and PRP-MSCs for 24 hours in transwell co-culture system, DMEM as a negative control. NRK-52E cells were harvested for apoptosis assay, Western blot, and quantitative real-time polymerase chain reaction (qRT-PCR). Then the number of MSCs exosomes stimulated by PRP was detected by confocal microscopy and Nanosight tracking analysis (NTA), PRP-MSCs-Ex (10mg/kg) and MSCs-Ex (10mg/kg) were injected intravenously, saline as control. The therapeutic effect of PRP-MSCs was evaluated by analyzing renal function (serum BUN, Creatinine), histopathological structure changes and apoptosis and proliferation of renal tubular cells. Results: In vivo and vitro studies confirmed that the PRP induced YAP nucleus expression to promoting the proliferation and reinforces the stemness of MSCs, and PRP could promoted the paracrine secretion of exosomes by MSCs to repair AKI though AKT/Rab27 pathway.Conclusions: Our results revealed that PRP stimulated MSCs paracrine pathway could effectively alleviate glycerin-induced acute kidney injury. Therefore, RPP pretreatment may be a new method to improve the therapeutic effect of MSCs.

scholarly journals Platelet-rich Plasma Enhanced MSCs Repair for Glycerin-induced Acute Kidney Injury via AKT/Rab27 Paracrine Pathway

2020 ◽  
Author(s):  
Cheng Ji ◽  
Jiahui Zhang ◽  
Hui Shi ◽  
wanzhu Liu ◽  
Fengtian Sun ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Platelet Rich Plasma ◽  
Kidney Injury ◽  
Human Umbilical Cord ◽  
Tubular Cells ◽  
Renal Tubular Cells

Abstract Background: Acute kidney injury (AKI) was defined by rapid deterioration of renal function, as a common complication in hospitalized patients. Among the recent therapeutic options, mesenchymal stem cells (MSCs) were considered a promising strategy for damaged tissues repair. Platelet rich plasma (PRP) regulates stromal cells to repair tissue damage through the release of growth factors. Here we proposed a possible therapeutic use of human umbilical cord mesenchymal stem cells stimulated by platelet-rich plasma (PRP-MSCs) in a murine model of acute renal injury generated by glycerin injection.Methods: In vivo, we constructed cisplatin-induced acute kidney injury rat models. On day 1 post injury, rat received a tail vein injection of 1×106 MSCs and 1×106 PRP-MSCs. All animals were sacrificed at Day 3 after glycerin injection. Renal function (serum BUN, Creatinine), histopathological structure changes and tubular cells apoptosis were evaluated. In vitro experiment, 50 μmol/L of glycerin treated NRK-52E for 12h were incubated with MSC or PRP-MSC for 24h in transwell co-culture system. Cells were harvested for apoptosis assay, immunofluorescence assay, western blot, and quantitative real-time polymerase chain reaction (qRT-PCR).Results: In vivo and vitro studies confirmed that the PRP induced YAP nucleus expression to promoting the proliferation and reinforces the stemness of MSCs, and stimulated the paracrine exosomes of MSCs by activating AKT/Rab27 signaling pathway to inhibiting the apoptosis of renal tubular cells. Conclusions: Our results revealed a novel potential use of PRP-MSCs as therapeutic strategy for acute kidney injury, highlighting the presence and role of the reno-protective factor PRP-MSCs.

scholarly journals Bioluminescence imaging to monitor the in vivo distribution of administered mesenchymal stem cells in acute kidney injury

2008 ◽  
Vol 295 (1) ◽  
pp. F315-F321 ◽  
Author(s):  
Florian Tögel ◽  
Ying Yang ◽  
Ping Zhang ◽  
Zhuma Hu ◽  
Christof Westenfelder
Keyword(s):  
Stem Cells ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Targeted Delivery ◽  
Cell Tracking ◽  
Bioluminescence Imaging ◽  
Kidney Injury ◽  
Organ Distribution ◽  
Cell Numbers

Effective and targeted delivery of cells to injured organs is critical to the development of cell therapies. However, currently available in vivo cell tracking methods still lack sufficient sensitivity and specificity. We examined, therefore, whether a highly sensitive and specific bioluminescence method is suitable to noninvasively image the organ distribution of administered mesenchymal stem cells (MSCs) in vivo. MSCs were transfected with a luciferase/neomycin phosphotransferase construct (luc/neo-MSC). Bioluminescence of these cells was measured (charge-coupled device camera) after treatment with luciferin, showing a linear increase of photon emission with rising cell numbers. To track these cells in vivo, groups of mice were injected with 1 × 105 luc/neo-MSCs/animal and imaged with bioluminescence imaging at various time points. Injection of cells in the suprarenal aorta showed diffuse distribution of cells in normal animals, whereas distinct localization to the kidneys was observed in mice with ischemia- and reperfusion-induced acute kidney injury (AKI). Intrajugular infusion of MSCs demonstrated predominant accumulation of cells in both lungs. In animals with AKI, detectable cell numbers declined over time, as assessed by bioluminescence imaging and confirmed by PCR, a process that was associated with low apoptosis levels of intrarenally located MSCs. In conclusion, the described bioluminescence technology provides a sensitive and safe tool for the repeated in vivo tracking of infused luc/neo-MSCs in all major organs. This method will be of substantial utility in the preclinical testing and design of cell therapeutic strategies in kidney and other diseases.

CXCR4-overexpressing bone marrow-derived mesenchymal stem cells improve repair of acute kidney injury

2013 ◽  
Vol 305 (7) ◽  
pp. F1064-F1073 ◽  
Author(s):  
Nanmei Liu ◽  
Andreas Patzak ◽  
Jinyuan Zhang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Acute Kidney Injury ◽  
Cell Death ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Caspase 3 ◽  
Kidney Injury ◽  
Nuclear Antigen ◽  
Tubular Cells

Transplantation of bone marrow-derived mesenchymal stem cells (BMSCs) can repair acute kidney injury (AKI), but with limited effect. We test the hypothesis that CXCR4 overexpression improves the repair ability of BMSCs and that this is related to increased homing of BMSCs and increased release of cytokines. Hypoxia/reoxygenation-pretreated renal tubular epithelial cells (HR-RTECs) were used. BMSCs, null-BMSCs, and CXCR4-BMSCs were cocultured with HR-RTECs. The number of migrating BMSCs was counted. Proliferating cell nuclear antigen (PCNA) expression, cell death, and expressions of cleaved caspase-3 and Bcl-2 in cocultured HR-RTECs were measured. Cytokeratin 18 (CK18) expression and cytokine secretions of the BMSCs cultured with HR-RTEC supernatant were detected. BMSC homing, renal function, proliferation, and cell death of tubular cells were assayed in the AKI mouse model. CXCR4-BMSCs showed a remarkable expression of CXCR4. Stromal cell-derived factor-1 in the HR-RTEC supernatant was increased. Migration of BMSCs was CXCR4-dependent. Proportions of CK18+ cells in BMSCs, null-BMSCs, and CXCR4-BMSCs showed no difference. However, CXCR4 overexpression in BMSCs stimulated secretion of bone morphogenetic protein-7, hepatocyte growth factor, and interleukin 10. The neutralizing anti-CXCR4 antibody AMD3100 abolished this. In cocultured HR-RTECs the proportions of PCNA+ cells and Bcl-2 expression were enhanced; however, the proportion of annexin V+ cells and expression of cleaved caspase-3 were reduced. The in vivo study showed increased homing of CXCR4-BMSCs in kidneys, which was associated with improved renal function, reduced acute tubular necrosis scoring, accelerated mitogenic response of tubular cells, and reduced tubular cell death. The enhanced homing and paracrine actions of BMSCs with CXCR4 overexpression suggest beneficial effects of such cells in BMSC-based therapy for AKI.

scholarly journals Mesenchymal Stem Cells in Renal Function Recovery after Acute Kidney Injury: Use of a Differentiating Agent in a Rat Model

2011 ◽  
Vol 20 (8) ◽  
pp. 1193-1208 ◽  
Author(s):  
Gaetano La Manna ◽  
Francesca Bianchi ◽  
Maria Cappuccilli ◽  
Giovanna Cenacchi ◽  
Lucia Tarantino ◽  
...  
Keyword(s):  
Stem Cells ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Renal Function ◽  
Rat Model ◽  
Kidney Injury ◽  
Renal Function Recovery ◽  
Function Recovery ◽  
Differentiating Agent

P0520EFFECT OF HUMAN UMBILICAL CORD MESENCHYMAL STEM CELLS ON SECONDARY ACUTE KIDNEY INJURY IN RATS WITH LIVER CIRRHOSIS

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yan Mi
Keyword(s):  
Stem Cells ◽  
Acute Kidney Injury ◽  
Mesenchymal Stem Cells ◽  
Treatment Group ◽  
Olive Oil ◽  
Umbilical Cord ◽  
Kidney Injury ◽  
Control Group ◽  
Human Umbilical Cord ◽  
Model Group

Abstract Background and Aims Acute kidney injury( AKI) is one of the most common complications of decompensated cirrhosis, and it primarily presents as a sharp decrease in glomerular filtration rate, rapid increase in serum creatinine( SCr) and urea nitrogen. And the search for specific and safe treatment has been a research hot spot in recent years. In this article, the effect of human umbilical cord mesenchymal stem cells on carbon tetrachloride (CCl4)-induced liver fibrosis (HF) in rats with acute kidney injury and the possible mechanism are investigated. Method Human umbilical cord blood mesenchymal stem cells were sub-cultured by adherent method, and the cells were identified by morphological observation, cell phenotypic analysis and multi-directional differentiation potential analysis methods. WASTA rats were randomly divided into control group, cirrhosis model group and treatment group, with 10 rats in each group. Model group and treatment group were injected with CCl4-olive oil (1:1) solution 3 mL·kg -1, and the control group was given the same amount of olive oil for intervention, twice a week for 8 weeks. Rats in treatment group were administrated wth Human umbilical cord mesenchymal stem cells (2 × 109 /L) via the tail vein at the 5th week after injection of CCl4-olive oil solution, but the other rats were injected with 0.9% normal saline, once a week for 6 weeks. After the intervention, Serum, kidneys and 24 hours urine of rats in each group were collected, which were applied for a detection of serum creatinine and urea nitrogen, malondialdehyde (MDA), NO content and superoxide dismutase (SOD), as well as renal pathological examination. Results 1.In vitro, umbilical cord blood mesenchymal stem cells was passaged to the third generation, and the morphology was uniform and spiraled. Phenotypic analysis showed that the positive rates of stem cell markers CD29, CD44 and CD105 were all greater than 95%, the positive rate of HLA-DR (graft-versus-host disease-associated factor) less than 10%, and the positive rate of CD34 and CD45 lower than 20% (Figure 1). 2. Compared with the cirrhotic model group, MDA content of serum and kidney in model group significantly decreased under the effect of mesenchymal stem cell (p <0.01) (Table 1). 3. The normal group had normal liver tissue structure, ordered liver cells, no hepatic edema, and no lesions. In the model group, large-area lesions, including edema of liver cells, rupture of cell membranes, and infiltration of inflammatory cells, had appeared. Compared with the model group, Hepatocellular necrosis, edema, and inflammatory cell infiltration were significantly improved after transplanting Human umbilical cord mesenchymal stem cells (Figure 2). 4.In the model group, the rat renal tubules disappeared and the lumen was disordered. After injection of Human umbilical cord mesenchymal stem cells, renal tubular and renal interstitial damage is improved and the thickening of glomerular basement membrane is reduced (Figure 3). Conclusion In CCl4-induced liver cirrhosis model rats, human umbilical cord mesenchymal stem cells can protect the kidney by reducing free radicals and cellular lipid peroxidation in vivo.

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