High-mobility group box 1 protein antagonizes the immunosuppressive capacity and therapeutic effect of mesenchymal stem cells in acute kidney injury

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.

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Faculty Opinions recommendation of Microvesicles derived from mesenchymal stem cells enhance survival in a lethal model of acute kidney injury.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717959864.793463065 ◽

2012 ◽

Author(s):

Michael Mayr ◽

Patrizia Amico

Keyword(s):

Stem Cells ◽

Acute Kidney Injury ◽

Mesenchymal Stem Cells ◽

Kidney Injury

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Comparative study of allogenic and xenogeneic mesenchymal stem cells on cisplatin-induced acute kidney injury in Sprague-Dawley rats

Stem Cell Research & Therapy ◽

10.1186/s13287-016-0386-0 ◽

2016 ◽

Vol 7 (1) ◽

Cited By ~ 21

Author(s):

Rehab H. Ashour ◽

Mohamed-Ahdy Saad ◽

Mohamed-Ahmed Sobh ◽

Fatma Al-Husseiny ◽

Mohamed Abouelkheir ◽

...

Keyword(s):

Stem Cells ◽

Acute Kidney Injury ◽

Mesenchymal Stem Cells ◽

Comparative Study ◽

Kidney Injury ◽

Sprague Dawley ◽

Sprague Dawley Rats

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Extracellular vesicles derived from mesenchymal stem cells as a potential therapeutic agent in acute kidney injury (AKI) in felines: review and perspectives

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02573-6 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Magdalena M. Kraińska ◽

Natalia Pietrzkowska ◽

Eliza Turlej ◽

Li Zongjin ◽

Krzysztof Marycz

Keyword(s):

Stem Cells ◽

Acute Kidney Injury ◽

Mesenchymal Stem Cells ◽

Extracellular Vesicles ◽

Kidney Injury ◽

Cargo Transport ◽

Potential Benefits ◽

Apoptotic Effects ◽

Different Sources ◽

Modern Tool

AbstractMesenchymal stem cells (MSCs), known from their key role in the regeneration process of tissues, and their abilities to release bioactive factors like extracellular vesicles (EVs) could be considered as a potential, modern tool in the treatment of AKI (acute kidney injury) in both human and veterinary patients. The complex pathophysiology of a renal function disorder (AKI) makes difficult to find a universal therapy, but the treatment strategy is based on MSCs and derived from them, EVs seem to solve this problem. Due to their small size, the ability of the cargo transport, the ease of crossing the barriers and the lack of the ability to proliferate and differentiate, EVs seem to have a significant impact on the development such therapy. Their additional impact associated with their ability to modulate immune response and inflammation process, their strong anti-fibrotic and anti-apoptotic effects and the relation with the releasing of the reactive oxygen species (ROS), that pivotal role in the AKI development is undoubtedly, limits the progress of AKI. Moreover, the availability of EVs from different sources encourages to extend research with using EVs from MSCs in AKI treatment in felines; in that, the possibilities of kidney injuries treatment are still limited to the classical therapies burdened with dangerous side effects. In this review, we underline the significance of the processes, in whose EVs are included during the AKI in order to show the potential benefits of EVs-MSCs-based therapies against AKI in felines.

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