<i>In Vivo</i> Tracking of Mesenchymal Stem Cell-Derived Extracellular Vesicles Improving Mitochondrial Function in Renal Ischemia–Reperfusion Injury

Cao, Hongmei; Cheng, Yuanqiu; Hong, Gao; Zhuang, Jie; Zhang, Weiguang; Bian, Qiang; Wang, Fang; Du, Yuan; Li, Zongjin; Kong, Deling; Ding, Dan; Wang, Yuebing

doi:10.1021/acsnano.9b08207

Cited by 139 publications

(126 citation statements)

References 39 publications

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“…MSCs were a promising therapeutic tool in regenerative medicine due to their self-renewal and multidirectional differentiation potency. Recently have a large number of studies showed that MSCs could repair cisplatin/glycerin-induced acute kidney injury [30] , ischemia/reperfusion-induced acute renal failure [31] , and unilateral ureteral obstruction-induced renal interstitial brosis [32] . Nevertheless, the transplanted MSCs also existed potential problem, most of them could not survive for a long time, only a few of them exist in the damaged kidney.…”

Section: Discussionmentioning

confidence: 99%

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

Zhang

Shi

et al. 2020

Preprint

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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.

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Section: Discussionmentioning

confidence: 99%

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

Zhang

Shi

et al. 2020

Preprint

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“…For instance, in tubular or renal injury, MSC-EVs regulated proliferative or anti-apoptotic pathways in tubular epithelial cells 113 , 114 , shuttled several pro-angiogenic transcription factors 115 , or suppressed CX3CL1 expression and reduced the subsequent infiltration of macrophages in the damaged kidney 116 . Recent in vivo studies further indicated that MSC-EVs promoted the recovery of kidney function in animal models of ischemia-reperfusion-induced acute kidney injury, which could be considered as a future potential therapy 117 . Moreover, some studies have reported that MSC-EVs could be used for the treatment of liver diseases, as MSC-EVs suppressed the epithelial-to-mesenchymal transition 118 , increased hepatocyte regeneration 119 , and decreased the proliferation of hepatic stellate cells 120 .…”

Section: Characteristics and Functions Of Evs From Cells Associated Wmentioning

confidence: 99%

Extracellular vesicles in Inflammatory Skin Disorders: from Pathophysiology to Treatment

Shao¹,

Fang²,

Li³

et al. 2020

Theranostics

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Extracellular vesicles (EVs), naturally secreted by almost all known cell types into extracellular space, can transfer their bioactive cargos of nucleic acids and proteins to recipient cells, mediating cell-cell communication. Thus, they participate in many pathogenic processes including immune regulation, cell proliferation and differentiation, cell death, angiogenesis, among others. Cumulative evidence has shown the important regulatory effects of EVs on the initiation and progression of inflammation, autoimmunity, and cancer. In dermatology, recent studies indicate that EVs play key immunomodulatory roles in inflammatory skin disorders, including psoriasis, atopic dermatitis, lichen planus, bullous pemphigoid, systemic lupus erythematosus, and wound healing. Importantly, EVs can be used as biomarkers of pathophysiological states and/or therapeutic agents, both as carriers of drugs or even as a drug by themselves. In this review, we will summarize current research advances of EVs from different cells and their implications in inflammatory skin disorders, and further discuss their future applications, updated techniques, and challenges in clinical translational medicine.

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“…As mitochondrial dysfunction is one important cause of OA (Blanco et al, 2011) and MSCs-EV are important for intercellular mitochondria communication (Cao et al, 2020), suggesting the possibility of MSCs-EV in treating OA by regulating mitochondria function. Mitochondrial dysfunction and oxidative stress damage are associated with apoptosis, senescence and various pathological conditions, which are hallmarks of OA.…”

Section: Cartilage Protection and Regeneration Effect Of Mscs-ev In Oamentioning

confidence: 99%

The Application of MSCs-Derived Extracellular Vesicles in Bone Disorders: Novel Cell-Free Therapeutic Strategy

Liu

Liang

et al. 2020

Front. Cell Dev. Biol.

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Bone is crucial for supporting the body, protecting other organs, providing minerals, and secreting hormone to regulate other organ's function. Bone disorders result in pain and disability, severely affecting human health, reducing the quality of life and increasing costs to society. With the rapid increase in the aging population worldwide, bone disorders have become one major disease. As a result, efficacious therapies of bone disorders have become the focus of attention worldwide. Mesenchymal stem cells (MSCs) have been widely explored as a new therapeutic method for numerous diseases. Recent evidence suggests that the therapeutic effects of MSCs are mainly mediated by their extracellular vesicles (EV). MSCs-derived extracellular vesicles (MSCs-EV) is indicated as a novel cell-free alternative to cell therapy with MSCs in regenerative medicine. Here, we review the current knowledge of EV and highlight the application studies of MSCs-EV in bone disorders by focusing on osteoarthritis (OA), rheumatoid arthritis (RA), osteoporosis (OP), and bone fracture. Moreover, we discuss the key issues and perspectives of MSCs-EV as a clinical therapeutic strategy for bone diseases.

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In Vivo Tracking of Mesenchymal Stem Cell-Derived Extracellular Vesicles Improving Mitochondrial Function in Renal Ischemia–Reperfusion Injury

Cited by 139 publications

References 39 publications

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

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

Extracellular vesicles in Inflammatory Skin Disorders: from Pathophysiology to Treatment

The Application of MSCs-Derived Extracellular Vesicles in Bone Disorders: Novel Cell-Free Therapeutic Strategy

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