scholarly journals Stem Cell-Derived Extracellular Vesicles and Kidney Regeneration

Cells ◽  
2019 ◽  
Vol 8 (10) ◽  
pp. 1240 ◽  
Author(s):  
Grange ◽  
Skovronova ◽  
Marabese ◽  
Bussolati
Keyword(s):  
Clinical Trials ◽  
Stem Cell ◽  
Extracellular Vesicles ◽  
Therapeutic Option ◽  
Genetic Material ◽  
Kidney Injury ◽  
Convincing Evidence ◽  
Apoptosis And Inflammation ◽  
Injury Models ◽  
New Strategies

Extracellular vesicles (EVs) are membranous vesicles containing active proteins, lipids, and different types of genetic material such as miRNAs, mRNAs, and DNAs related to the characteristics of the originating cell. They possess a distinctive capacity to communicate over long distances. EVs have been involved in the modulation of several pathophysiological conditions and, more importantly, stem cell-derived EVs appear as a new promising therapeutic option. In fact, several reports provide convincing evidence of the regenerative potential of EVs released by stem cells and, in particular, mesenchymal stromal cells (MSCs) in different kidney injury models. Described mechanisms involve the reprogramming of injured cells, cell proliferation and angiogenesis, and inhibition of cell apoptosis and inflammation. Besides, the therapeutic use of MSC-EVs in clinical trials is under investigation. This review will focus on MSC-EV applications in preclinical models of acute and chronic renal damage including recent data on their use in kidney transplant conditioning. Moreover, ongoing clinical trials are described. Finally, new strategies to broaden and enhance EV therapeutic efficacy by engineering are discussed.

scholarly journals Regenerative Role of Stem Cell-Derived Extracellular Vesicles in Acute Kidney Injury

Nephron ◽  
2020 ◽  
Vol 144 (12) ◽  
pp. 638-643
Author(s):  
Davide Medica ◽  
Sergio Dellepiane ◽  
Vincenzo Cantaluppi
Keyword(s):  
Acute Kidney Injury ◽  
Clinical Trials ◽  
Extracellular Vesicles ◽  
Therapeutic Option ◽  
Kidney Injury ◽  
Glomerular Injury ◽  
Paracrine Factors ◽  
Short And Long Term

Acute kidney injury (AKI) is a frequent complication of hospital admission and worsens short- and long-term patients’ prognosis. Currently, AKI treatment remains supportive and no therapy has proven significant benefit in clinical trials. Stem cells (SCs) are a promising therapeutic option, but their translation to the clinical setting is limited by the risk of rejection or aberrant differentiation. Numerous studies have shown how SC effects are mediated by paracrine factors such as extracellular vesicles (EVs). In this review, we describe the preclinical evidence about EV efficacy in acute tubular and glomerular injury and the recently generated clinical data.

scholarly journals Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

2021 ◽  
Vol 10 (4) ◽  
pp. 711
Author(s):  
Byung-Chul Lee ◽  
Insung Kang ◽  
Kyung-Rok Yu
Keyword(s):  
Clinical Trials ◽  
Therapeutic Agent ◽  
Therapeutic Potential ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Genetic Material ◽  
Experimental Models ◽  
Attractive Alternative ◽  
Cell Based Therapy ◽  
Cellular Rejection

Identification of the immunomodulatory and regenerative properties of mesenchymal stem cells (MSCs) have made them an attractive alternative therapeutic option for diseases with no effective treatment options. Numerous clinical trials have followed; however, issues such as infusional toxicity and cellular rejection have been reported. To address these problems associated with cell-based therapy, MSC exosome therapy was developed and has shown promising clinical outcomes. MSC exosomes are nanosized vesicles secreted from MSCs and represent a non-cellular therapeutic agent. MSC exosomes retain therapeutic features of the cells from which they originated including genetic material, lipids, and proteins. Similar to MSCs, exosomes can induce cell differentiation, immunoregulation, angiogenesis, and tumor suppression. MSC exosomes have therefore been employed in several experimental models and clinical studies. Here, we review the therapeutic potential of MSC-derived exosomes and summarize currently ongoing clinical trials according to disease type. In addition, we propose several functional enhancement strategies for the effective clinical application of MSC exosome therapy.

scholarly journals Embryonic stem cell-derived extracellular vesicles promote the recovery of kidney injury

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Lu Yu ◽  
Siying Liu ◽  
Chen Wang ◽  
Chuanyu Zhang ◽  
Yajie Wen ◽  
...  
Keyword(s):  
Stem Cell ◽  
Embryonic Stem Cell ◽  
Extracellular Vesicles ◽  
Therapeutic Potential ◽  
Es Cells ◽  
Ischemia Reperfusion ◽  
Embryonic Stem ◽  
Kidney Injury ◽  
Structure And Function ◽  
And Function

Abstract Background Embryonic stem cell-derived extracellular vesicles (ESC-EVs) possess therapeutic potential for a variety of diseases and are considered as an alternative of ES cells. Acute kidney injury (AKI) is a common acute and severe disease in clinical practice, which seriously threatens human life and health. However, the roles and mechanisms of ESC-EVs on AKI remain unclear. Methods In this study, we evaluated the effects of ESC-EVs on physiological repair and pathological repair using murine ischemia-reperfusion injury-induced AKI model, the potential mechanisms of which were next investigated. EVs were isolated from ESCs and EVs derived from mouse fibroblasts as therapeutic controls. We then investigated whether ESC-EVs can restore the structure and function of the damaged kidney by promoting physiological repair and inhibiting the pathological repair process after AKI in vivo and in vitro. Results We found that ESC-EVs significantly promoted the recovery of the structure and function of the damaged kidney. ESC-EVs increased the proliferation of renal tubular epithelial cells, facilitated renal angiogenesis, inhibited the progression of renal fibrosis, and rescued DNA damage caused by ischemia and reperfusion after AKI. Finally, we found that ESC-EVs play a therapeutic effect by activating Sox9+ cells. Conclusions ESC-EVs significantly promote the physiological repair and inhibit the pathological repair after AKI, enabling restoration of the structure and function of the damaged kidney. This strategy might emerge as a novel therapeutic strategy for ESC clinical application.

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 MRI tracking reveals selective accumulation of stem cell-derived magneto-extracellular vesicles in sites of injury

2019 ◽  
Author(s):  
Zheng Han ◽  
Senquan Liu ◽  
Yigang Pei ◽  
Zheng Ding ◽  
Yuguo Li ◽  
...  
Keyword(s):  
Stem Cell ◽  
Extracellular Vesicles ◽  
Kidney Injury ◽  
Induced Pluripotent Stem Cell ◽  
Superparamagnetic Iron Oxide ◽  
Whole Body ◽  
Body Distribution ◽  
Magnetic Resonance Imaging Mri ◽  
Induced Pluripotent

AbstractHuman stem-cell-derived extracellular vesicles (EVs) are currently being investigated for cell-free therapy in regenerative medicine applications, but their biodistribution and tropic properties for homing to injured tissues are largely unknown. Here, we labeled EVs with magnetic nanoparticles to create magneto-EVs that can be tracked by magnetic resonance imaging (MRI). Superparamagnetic iron oxide (SPIO) nanoparticles were coated with polyhistidine tags, which enabled purification of labeled EVs by efficiently removing unencapsulated SPIO particles in the solution. The biodistribution of systemically injected human induced pluripotent stem cell (iPSC)-derived magneto-EV was assessed in three different animal models of kidney injury and myocardial ischemia. Magneto-EVs were found to selectively home to the injury sites and conferred substantial protection in a kidney injury model. In vivo MRI tracking of magnetically labeled EVs represents a new powerful method to assess and quantify their whole-body distribution, which may help optimize further development of EV-based cell-free therapy.

scholarly journals Human Liver Stem Cell Derived Extracellular Vesicles Alleviate Kidney Fibrosis by Interfering with the β-Catenin Pathway through miR29b

2021 ◽  
Vol 22 (19) ◽  
pp. 10780
Author(s):  
Sharad Kholia ◽  
Maria Beatriz Herrera Sanchez ◽  
Maria Chiara Deregibus ◽  
Marco Sassoè-Pognetto ◽  
Giovanni Camussi ◽  
...  
Keyword(s):  
Stem Cell ◽  
Extracellular Vesicles ◽  
Human Liver ◽  
Kidney Injury ◽  
Loss Of Function ◽  
Kidney Fibrosis ◽  
Clinical Models ◽  
Collagen Type 1

Human liver stem-cell-derived extracellular vesicles (HLSC-EVs) exhibit therapeutic properties in various pre-clinical models of kidney injury. We previously reported an overall improvement in kidney function following treatment with HLSC-EVs in a model of aristolochic acid nephropathy (AAN). Here, we provide evidence that HLSC-EVs exert anti-fibrotic effects by interfering with β-catenin signalling. A mouse model of AAN and an in vitro pro-fibrotic model were used. The β-catenin mRNA and protein expression, together with the pro-fibrotic markers α-SMA and collagen 1, were evaluated in vivo and in vitro following treatment with HLSC-EVs. Expression and functional analysis of miR29b was performed in vitro following HLSC-EV treatments through loss-of-function experiments. Results showed that expression of β-catenin was amplified both in vivo and in vitro, and β-catenin gene silencing in fibroblasts prevented AA-induced up-regulation of pro-fibrotic genes, revealing that β-catenin is an important factor in fibroblast activation. Treatment with HLSC-EVs caused increased expression of miR29b, which was significantly inhibited in the presence of α-amanitin. The suppression of the miR29b function with a selective inhibitor abolished the anti-fibrotic effects of HLSC-EVs, resulting in the up-regulation of β-catenin and pro-fibrotic α-Sma and collagen type 1 genes. Together, these data suggest a novel HLSC-EV-dependent regulatory mechanism in which β-catenin is down regulated by HLSC-EVs-induced miR29b expression.

scholarly journals Coassembly of hypoxia-sensitive macrocyclic amphiphiles and extracellular vesicles for targeted kidney injury imaging and therapy

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Yuan-Qiu Cheng ◽  
Yu-Xin Yue ◽  
Hong-Mei Cao ◽  
Wen-Chao Geng ◽  
Lan-Xing Wang ◽  
...  
Keyword(s):  
Extracellular Vesicles ◽  
Self Assembly ◽  
Near Infrared ◽  
Ischemia Reperfusion Injury ◽  
Kidney Diseases ◽  
Therapeutic Option ◽  
Ischemia Reperfusion ◽  
Kidney Injury ◽  
M2 Macrophage ◽  
Novel Strategy

Abstract Background Hypoxia is a major contributor to global kidney diseases. Targeting hypoxia is a promising therapeutic option against both acute kidney injury and chronic kidney disease; however, an effective strategy that can achieve simultaneous targeted kidney hypoxia imaging and therapy has yet to be established. Herein, we fabricated a unique nano-sized hypoxia-sensitive coassembly (Pc/C5A@EVs) via molecular recognition and self-assembly, which is composed of the macrocyclic amphiphile C5A, the commercial dye sulfonated aluminum phthalocyanine (Pc) and mesenchymal stem cell-excreted extracellular vesicles (MSC-EVs). Results In murine models of unilateral or bilateral ischemia/reperfusion injury, MSC-EVs protected the Pc/C5A complex from immune metabolism, prolonged the circulation time of the complex, and specifically led Pc/C5A to hypoxic kidneys via surface integrin receptor α4β1 and αLβ2, where Pc/C5A released the near-infrared fluorescence of Pc and achieved enhanced hypoxia-sensitive imaging. Meanwhile, the coassembly significantly recovered kidney function by attenuating cell apoptosis, inhibiting the progression of renal fibrosis and reducing tubulointerstitial inflammation. Mechanistically, the Pc/C5A coassembly induced M1-to-M2 macrophage transition by inhibiting the HIF-1α expression in hypoxic renal tubular epithelial cells (TECs) and downstream NF-κB signaling pathway to exert their regenerative effects. Conclusion This synergetic nanoscale coassembly with great translational potential provides a novel strategy for precise kidney hypoxia diagnosis and efficient kidney injury treatment. Furthermore, our strategy of coassembling exogenous macrocyclic receptors with endogenous cell-derived membranous structures may offer a functional platform to address multiple clinical needs. Graphical Abstract

scholarly journals How to Improve the Survival of Transplanted Mesenchymal Stem Cell in Ischemic Heart?

2016 ◽  
Vol 2016 ◽  
pp. 1-14 ◽  
Author(s):  
Liangpeng Li ◽  
Xiongwen Chen ◽  
Wei Eric Wang ◽  
Chunyu Zeng
Keyword(s):  
Clinical Trials ◽  
Animal Model ◽  
Stem Cell ◽  
Mesenchymal Stem Cell ◽  
Heart Tissue ◽  
Cardiac Repair ◽  
Ischemic Heart ◽  
Cell Type ◽  
New Strategies ◽  
Stem Cell Type

Mesenchymal stem cell (MSC) is an intensely studied stem cell type applied for cardiac repair. For decades, the preclinical researches on animal model and clinical trials have suggested that MSC transplantation exerts therapeutic effect on ischemic heart disease. However, there remain major limitations to be overcome, one of which is the very low survival rate after transplantation in heart tissue. Various strategies have been tried to improve the MSC survival, and many of them showed promising results. In this review, we analyzed the studies in recent years to summarize the methods, effects, and mechanisms of the new strategies to address this question.

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