The Multi-Therapeutic Role of MSCs in Diabetic Nephropathy

Wang, Yi; Shan, Su-Kang; Guo, Bei; Li, Fuxingzi; Zheng, Minghui; Lei, Li-Min; Xu, Qiu-Shuang; Ullah, Muhammad Hasnain Ehsan; Xu, Feng; Lin, Xiao; Yuan, Ling‐Qing

doi:10.3389/fendo.2021.671566

Cited by 23 publications

(18 citation statements)

References 129 publications

(129 reference statements)

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“…An increasing body of evidence suggests that MSC-based therapy can improve patient outcomes in DKD treatment, including decreasing proteinuria, improving renal function, and alleviating renal fibrosis. [28][29][30] At present, there is ample evidence that MSCs mainly exert therapeutic effects through exosomes-mediated paracrine mechanisms. 31 It has been suggested that MSC-exos can fix cisplatin-induced AKI in rats and NRK-52E cell injury by ameliorating oxidative stress and cell apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Exosomes derived from mesenchymal stem cells attenuate diabetic kidney disease by inhibiting cell apoptosis and epithelial‐to‐mesenchymal transition via miR‐424‐5p

et al. 2022

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Diabetic kidney disease (DKD) is well-acknowledged as one of the most common complications in diabetes mellitus. Recent studies have demonstrated the promising role of mesenchymal stem cell-derived exosomes (MSC-exos) as a cell-free treatment strategy for DKD. The present study sought to investigate the therapeutic potential and the underlying mechanisms of MSC-exos in DKD. The authentication of MSC-exos was validated by western blot, transmission electron microscope (TEM), and nanosight tracking analysis (NTA). Apoptosis was detected by western blot, TUNEL staining, and flow cytometry. Epithelialto-mesenchymal transition (EMT) was evaluated by western blot and immunofluorescence. The relationship between miR-424-5p and Yes-associated protein 1 (YAP1) was revealed by dual luciferase reporter assay. We observed that MSCexos could attenuate DKD by decreasing cell apoptosis and inhibiting epithelialto-mesenchymal transition (EMT) in diabetic kidneys in db/db mice. Besides, we documented that MSC-exos could reverse high glucose-induced apoptosis and EMT in HK2 cells. Interestingly, miR-424-5p derived from MSC-exos could inhibit YAP1 activation in HK2 cells, resulting in alleviation of high glucose-induced cell apoptosis and EMT. Our study provides novel insights into MSC-exos-mediated protective effect in DKD. MSC-exos could inhibit high glucose-induced apoptosis and EMT through miR-424-5p targeting of YAP1.

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Section: Discussionmentioning

confidence: 99%

Exosomes derived from mesenchymal stem cells attenuate diabetic kidney disease by inhibiting cell apoptosis and epithelial‐to‐mesenchymal transition via miR‐424‐5p

et al. 2022

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“…Currently, the clinical treatment is to slow down DN progression by administering drugs that improve blood pressure or blood glucose levels. Once DN progresses to irreversible stages, alternative treatments such as hemodialysis are inevitable 77 . Li et al 78 reported that mouse umbilical cord MSCs (MUC-MSCs) blocked transforming growth factor-β(TGF-β)-triggered myofibroblast transdifferentiation through paracrine sEVs, inhibited PI3K/Akt and mitogen-activated protein kinase (MAPK) signaling-mediated mesangial cell proliferation, increased matrix metalloproteinase levels in mesangial cells, and reduced renal fibrosis in a DN mouse model.…”

Section: Msc-sevs In Kidney Diseasementioning

confidence: 99%

Mesenchymal Stem Cell-Derived Small Extracellular Vesicles: A Novel Approach for Kidney Disease Treatment

Lu¹,

Wang²,

Zhang³

et al. 2022

IJN

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Globally, kidney disease has become a serious health challenge, with approximately 10% of adults suffering with the disease, and increasing incidence and mortality rates every year. Small extracellular vesicles (sEVs) are 30 nm–100 nm sized nanovesicles released by cells into the extracellular matrix (ECM), which serve as mediators of intercellular communication. Depending on the cell origin, sEVs have different roles which depend on internal cargoes including, nucleic acids, proteins, and lipids. Mesenchymal stem cell (MSCs) exert anti-inflammatory, anti-aging, and wound healing functions mainly via sEVs in a stable and safe manner. MSC-derived sEVs (MSC-sEVs) exert roles in several kidney diseases by transporting renoprotective cargoes to reduce oxidative stress, inhibit renal cell apoptosis, suppress inflammation, and mediate anti-fibrosis mechanisms. Additionally, because MSC-sEVs efficiently target damaged kidneys, they have the potential to become the next generation cell-free therapies for kidney disease. Herein, we review recent research data on how MSC-sEVs could be used to treat kidney disease.

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“…However, the incidence of end-stage renal disease remains high. BMSCs-Exos have been proven to participate in slowing down the progression of DN by controlling hyperglycemia and protecting kidney function [ 141 ]. In addition, exosomes derived from ADSCs and hucMSCs have also been confirmed to be used for the treatment of DN [ 146 , 147 ] ( Table 2 ).…”

Section: Evs In Aging-related Diseasesmentioning

confidence: 99%

“…Diabetic Nephropathy. Diabetic nephropathy (DN) is one of the microvascular complications of DM, which causes end-stage renal disease [141]. Its clinical diagnosis mainly depends on the presence of proteinuria and the estimated decrease in the glomerular filtration rate [142].…”

Section: Roles Of Evs In Dm and Itsmentioning

confidence: 99%

Diagnostic and Therapeutic Roles of Extracellular Vesicles in Aging-Related Diseases

Sun

Hou

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Aging shows a decline in overall physical function, and cellular senescence is the powerful catalyst leading to aging. Considering that aging will be accompanied with the emergence of various aging-related diseases, research on new antiaging drugs is still valuable. Extracellular vesicles (EVs), as tools for intercellular communication, are important components of the senescence-associated secretory phenotype (SASP), and they can play pathological roles in the process of cellular senescence. In addition, EVs are similar to their original cells in functions. Therefore, EVs derived from pathological tissues or body fluids may be closely related to the progression of diseases and become potential biomarkers, while those from healthy cells may have therapeutic effects. Moreover, EVs are satisfactory drug carriers. At present, numerous studies have supported the idea that engineered EVs could improve drug targeting ability and utilization efficiency. Here, we summarize the characteristics of EVs and cellular senescence and focus on the diagnostic and therapeutic potential of EVs in various aging-related diseases, including Alzheimer disease, osteoporosis, cardiovascular disease, diabetes mellitus and its complications, and skin aging.

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The Multi-Therapeutic Role of MSCs in Diabetic Nephropathy

Cited by 23 publications

References 129 publications

Exosomes derived from mesenchymal stem cells attenuate diabetic kidney disease by inhibiting cell apoptosis and epithelial‐to‐mesenchymal transition via miR‐424‐5p

Exosomes derived from mesenchymal stem cells attenuate diabetic kidney disease by inhibiting cell apoptosis and epithelial‐to‐mesenchymal transition via miR‐424‐5p

Mesenchymal Stem Cell-Derived Small Extracellular Vesicles: A Novel Approach for Kidney Disease Treatment

Diagnostic and Therapeutic Roles of Extracellular Vesicles in Aging-Related Diseases

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