scholarly journals Mesenchymal Stem Cell Derived Extracellular Vesicles Ameliorate Kidney Injury in Aristolochic Acid Nephropathy

2020 ◽  
Vol 8 ◽  
Author(s):  
Sharad Kholia ◽  
Maria Beatriz Herrera Sanchez ◽  
Massimo Cedrino ◽  
Elli Papadimitriou ◽  
Marta Tapparo ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Aristolochic Acid ◽  
Kidney Injury ◽  
Aristolochic Acid Nephropathy

scholarly journals Oct-4 Enhanced the Therapeutic Effects of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Acute Kidney Injury

2020 ◽  
Vol 45 (1) ◽  
pp. 95-108 ◽  
Author(s):  
Zhi-Yuan  Zhang ◽  
Yan-Ping Hou ◽  
Xiang-Yu Zou ◽  
Xiao-Yu Xing ◽  
Guan-Qun Ju ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
Nuclear Antigen ◽  
Vehicle Group ◽  
Tunel Staining ◽  
Therapeutic Effects

Background/Aims: Acute kidney injury (AKI) is a common clinical condition that can lead to chronic kidney failure. Although mesenchymal stem cell-derived extracellular vesicles (MSC EVs) are regarded as a potent AKI treatment, the mechanisms underlying their beneficial effects remain unclear. Oct-4 may play an important role in tissue injury repair. We thus hypothesized that oct-4 overexpression might enhance the therapeutic effects of MSC EVs in AKI treatment. Methods: Renal tubular epithelial cells were cultured in a low oxygen environment, then cocultured with MSC EVs or control medium for 48 h. BrdU and transferase-mediated dUTP nick-end labeling (TUNEL) staining were used to assess cell proliferation and apoptosis. Mice subjected to ischemia reperfusion were randomly divided into 4 groups, then injected with either phosphate-buffered saline (vehicle), EVs, EVs overexpressing oct-4 (EVs+Oct-4), and EVs not expressing Oct-4 (EVs–Oct-4). Blood creatinine (CREA) and urine nitrone levels were assessed 48 h and 2 weeks after injection. After ischemia reperfusion, renal tissues from each group were stained with TUNEL and proliferating cell nuclear antigen (PCNA) to determine the degree of apoptosis and proliferation. Masson trichrome staining was used to evaluate renal fibrosis progression. Snail gene expression was assessed using polymerase chain reaction (PCR). Results: At 48 h after hypoxic treatment, TUNEL and BrdU staining indicated that the EVs+Oct-4 group had the least apoptosis and the most proliferation, respectively. Treatment with EVs overexpressing Oct-4 significantly decreased serum Crea and blood urea nitrogen levels and rescued kidney fibrosis, as indicated by the low proportion of Masson staining, high number of PCNA-positive cells, and low number of TUNEL-positive cells. PCR analysis indicated that Snail was most upregulated in the vehicle group and least upregulated in the EVs+Oct-4 group. Conclusions: MSC EVs had a pronounced therapeutic effect on ischemic reperfusion injury-related AKI, and Oct-4 overexpression enhanced these therapeutic effects. Our results may inspire a new direction for AKI treatment with MSC EVs.

scholarly journals Biodistribution of mesenchymal stem cell-derived extracellular vesicles in a model of acute kidney injury monitored by optical imaging

2014 ◽  
Vol 33 (5) ◽  
pp. 1055-1063 ◽  
Author(s):  
CRISTINA GRANGE ◽  
MARTA TAPPARO ◽  
STEFANIA BRUNO ◽  
DEVASIS CHATTERJEE ◽  
PETER J. QUESENBERRY ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Optical Imaging ◽  
Extracellular Vesicles ◽  
Kidney Injury

scholarly journals Uptake and Distribution of Administered Bone Marrow Mesenchymal Stem Cell Extracellular Vesicles in Retina

Cells ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 730
Author(s):  
Biji Mathew ◽  
Leianne A. Torres ◽  
Lorea Gamboa Gamboa Acha ◽  
Sophie Tran ◽  
Alice Liu ◽  
...  
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Time Course ◽  
Ganglion Cells ◽  
Ex Vivo ◽  
Dependent Manner ◽  
Paracrine Effects

Cell replacement therapy using mesenchymal (MSC) and other stem cells has been evaluated for diabetic retinopathy and glaucoma. This approach has significant limitations, including few cells integrated, aberrant growth, and surgical complications. Mesenchymal Stem Cell Exosomes/Extracellular Vesicles (MSC EVs), which include exosomes and microvesicles, are an emerging alternative, promoting immunomodulation, repair, and regeneration by mediating MSC’s paracrine effects. For the clinical translation of EV therapy, it is important to determine the cellular destination and time course of EV uptake in the retina following administration. Here, we tested the cellular fate of EVs using in vivo rat retinas, ex vivo retinal explant, and primary retinal cells. Intravitreally administered fluorescent EVs were rapidly cleared from the vitreous. Retinal ganglion cells (RGCs) had maximal EV fluorescence at 14 days post administration, and microglia at 7 days. Both in vivo and in the explant model, most EVs were no deeper than the inner nuclear layer. Retinal astrocytes, microglia, and mixed neurons in vitro endocytosed EVs in a dose-dependent manner. Thus, our results indicate that intravitreal EVs are suited for the treatment of retinal diseases affecting the inner retina. Modification of the EV surface should be considered for maintaining EVs in the vitreous for prolonged delivery.

scholarly journals Experimental artefacts can lead to misattribution of bioactivity from soluble mesenchymal stem cell paracrine factors to extracellular vesicles

2020 ◽  
Vol 9 (1) ◽  
pp. 1807674 ◽  
Author(s):  
Thomas E. Whittaker ◽  
Anika Nagelkerke ◽  
Valeria Nele ◽  
Ulrike Kauscher ◽  
Molly M. Stevens
Keyword(s):  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Extracellular Vesicles ◽  
Paracrine Factors
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