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

Lu, Yu; Liu, Siying; Wang, Chen; Zhang, Chuanyu; Wen, Yajie; Zhang, Kaiyue; Shang, Chaoqun; Hu, Huang; Liu, Yue; Wu, Lingling; Han, Zhongchao; Chen, Xiangmei; Li, Zongjin; Liu, Na

doi:10.1186/s13287-021-02460-0

Cited by 22 publications

(14 citation statements)

References 96 publications

(89 reference statements)

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“…The identified EVs were lysed and then the total protein content was determined using the bicinchoninic acid (BCA) protein quantification kit (BL-FZ-1008, Bio-light Biotech, Shanghai, China). The protein content was regarded as the standard of EVs [ 40 , 41 ].…”

Section: Methodsmentioning

confidence: 99%

Heterogeneous nuclear ribonucleoprotein U-actin complex derived from extracellular vesicles facilitates proliferation and migration of human coronary artery endothelial cells by promoting RNA polymerase II transcription

et al. 2022

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Coronary artery disease (CAD) represents a fatal public threat. The involvement of extracellular vesicles (EVs) in CAD has been documented. This study explored the regulation of embryonic stem cells (ESCs)-derived EVs-hnRNPU-actin complex in human coronary artery endothelial cell (HCAEC) growth. Firstly, in vitro HCAEC hypoxia models were established. EVs were extracted from ESCs by ultracentrifugation. HCAECs were treated with EVs and si-VEGF for 24 h under hypoxia, followed by assessment of cell proliferation, apoptosis, migration, and tube formation. Uptake of EVs by HCAECs was testified. Additionally, hnRNPU, VEGF, and RNA Pol II levels were determined using Western blotting and CHIP assays. Interaction between hnRNPU and actin was evaluated by Co-immunoprecipitation assay. HCAEC viability and proliferation were lowered, apoptosis was enhanced, wound fusion was decreased, and the number of tubular capillary structures was reduced under hypoxia, whereas ESC-EVs treatment counteracted these effects. Moreover, EVs transferred hnRNPU into HCAECs. EVs-hnRNPU-actin complex increased RNA Pol II level on the VEGF gene promoter and promoted VEGF expression in HCAECs. Inhibition of hnRNPU or VEGF both annulled the promotion of EVs on HCAEC growth. Collectively, ESC-EVs-hnRNPU-actin increased RNA Pol II phosphorylation and VEGF expression, thus promoting HCAEC growth.

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Section: Methodsmentioning

confidence: 99%

Heterogeneous nuclear ribonucleoprotein U-actin complex derived from extracellular vesicles facilitates proliferation and migration of human coronary artery endothelial cells by promoting RNA polymerase II transcription

et al. 2022

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“…These findings are important because even a single episode of AKI can increase the risk of developing CKD or accelerate the progression of existing CKD 93 . Extracellular vesicles isolated from embryonic stem cells have also been shown to promote kidney repair following AKI 94 . An advantage of these cells is that they can proliferate indefinitely in vitro, enabling continuous isolation of extracellular vesicles 94 .…”

Section: Therapeutic Use Of Extracellular Vesiclesmentioning

confidence: 99%

“…Extracellular vesicles isolated from embryonic stem cells have also been shown to promote kidney repair following AKI 94 . An advantage of these cells is that they can proliferate indefinitely in vitro, enabling continuous isolation of extracellular vesicles 94 . Studies using extracellular vesicles derived from endothelial progenitor cells and endothelial colony-forming cells have also reported protective effects in various models of kidney injury 23 , 95 – 97 .…”

Section: Therapeutic Use Of Extracellular Vesiclesmentioning

confidence: 99%

Extracellular vesicles in kidney disease

Grange

Bussolati

2022

Nat Rev Nephrol

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Extracellular vesicles are released by the majority of cell types and circulate in body fluids. They function as a long-distance cell-to-cell communication mechanism that modulates the gene expression profile and fate of target cells. Increasing evidence has established a central role of extracellular vesicles in kidney physiology and pathology. Urinary extracellular vesicles mediate crosstalk between glomerular and tubular cells and between different segments of the tubule, whereas circulating extracellular vesicles mediate organ crosstalk and are involved in the amplification of kidney damage and inflammation. The molecular profile of extracellular vesicles reflects the type and pathophysiological status of the originating cell so could potentially be exploited for diagnostic and prognostic purposes. In addition, robust preclinical data suggest that administration of exogenous extracellular vesicles could promote kidney regeneration and reduce inflammation and fibrosis in acute and chronic kidney diseases. Stem cells are thought to be the most promising source of extracellular vesicles with regenerative activity. Extracellular vesicles are also attractive candidates for drug delivery and various engineering strategies are being investigated to alter their cargo and increase their efficacy. However, rigorous standardization and scalable production strategies will be necessary to enable the clinical application of extracellular vesicles as potential therapeutics.

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“…Transplantation of embryonic [191] and MSC-derived [189] EVs was beneficial in preclinical AKI and CKD [189]. MSC-derived EVs accumulated in injury sites [192], where they induced proximal tubular cell proliferation and dedifferentiation and angiogenesis.…”

Section: Stem Cells and The Reparative Secretomementioning

confidence: 99%

Molecular Mechanisms of Kidney Injury and Repair

Rayego‐Mateos

Márquez‐Expósito

Rodrigues‐Díez

et al. 2022

IJMS

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Chronic kidney disease (CKD) will become the fifth global cause of death by 2040, thus emphasizing the need to better understand the molecular mechanisms of damage and regeneration in the kidney. CKD predisposes to acute kidney injury (AKI) which, in turn, promotes CKD progression. This implies that CKD or the AKI-to-CKD transition are associated with dysfunctional kidney repair mechanisms. Current therapeutic options slow CKD progression but fail to treat or accelerate recovery from AKI and are unable to promote kidney regeneration. Unraveling the cellular and molecular mechanisms involved in kidney injury and repair, including the failure of this process, may provide novel biomarkers and therapeutic tools. We now review the contribution of different molecular and cellular events to the AKI-to-CKD transition, focusing on the role of macrophages in kidney injury, the different forms of regulated cell death and necroinflammation, cellular senescence and the senescence-associated secretory phenotype (SAPS), polyploidization, and podocyte injury and activation of parietal epithelial cells. Next, we discuss key contributors to repair of kidney injury and opportunities for their therapeutic manipulation, with a focus on resident renal progenitor cells, stem cells and their reparative secretome, certain macrophage subphenotypes within the M2 phenotype and senescent cell clearance.

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

Cited by 22 publications

References 96 publications

Heterogeneous nuclear ribonucleoprotein U-actin complex derived from extracellular vesicles facilitates proliferation and migration of human coronary artery endothelial cells by promoting RNA polymerase II transcription

Heterogeneous nuclear ribonucleoprotein U-actin complex derived from extracellular vesicles facilitates proliferation and migration of human coronary artery endothelial cells by promoting RNA polymerase II transcription

Extracellular vesicles in kidney disease

Molecular Mechanisms of Kidney Injury and Repair

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