Extracellular vesicles from human urine-derived stem cells inhibit glucocorticoid-induced osteonecrosis of the femoral head by transporting and releasing pro-angiogenic DMBT1 and anti-apoptotic TIMP1

Chen, Chun-Yuan; Du, Wei; Rao, Shan‐Shan; Tan, Yuyong; Hu, Xiaozhou; Ou, Qifeng; Wu, Panfeng; Qing, Liming; Cao, Zheming; Yin, Hao; Tao, Yue; Zhan, Chaohong; Huang, Jie; Zhang, Yan; Liu, Yiwei; Wang, Zhenxing; Liu, Zhengzhao; Cao, Jia; Liu, Jianghua; Hong, Chengyu; He, Zehui; Yang, Jin; Tang, Siyuan; Tang, Juyu; Xie, Hui

doi:10.1016/j.actbio.2020.05.020

Cited by 37 publications

(46 citation statements)

References 53 publications

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“…Emerging evidence showed stem cellderived exosomes involved in angiogenesis. For instance, human urine-derived stem cell exosomes alleviate ONFH by reversing the GC-induced inhibition of endothelial angiogenesis [31]. HIF-1α modi ed rabbit BMSC exosomes induced neovascularization by promoting the HUVEC cell ability, migration, and tube formation [32].…”

Section: Discussionmentioning

confidence: 99%

MiR-150-5p-modified Bone Marrow Mesenchymal Stem Cells Derived Exosomes Ameliorate Osteonecrosis of Femoral Head by Promoting Endothelial Cell Angiogenesis

Fang¹,

He²,

Jiang³

et al. 2020

Preprint

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Background: Osteonecrosis of femoral head (ONFH) is a common ischemic disease that induces femoral head necrosis. The role of exosomes and miRNA in ONFH has been elucidated, however, whether miRNA-modified exosomes improve the therapy of ONFH is not clear.Methods: We screened ONFH-related miRNAs by RNA sequencing in plasma exosomes of ONFH patients and healthy donors. The key miRNA was overexpressed in bone marrow mesenchymal stem cells (BMSC) exosomes. The regulatory functions of miRNA-modified BMSC exosomes in vascular endothelial cells were illustrated through angiogenesis assay and scratch assay.Results: We identified 9 differently expressed miRNAs (DEmiRNAs) in plasma exosomes between ONFH and healthy groups, with 6 up-regulated and 3 down-regulated miRNAs. Function and pathway analysis revealed DEmiRNAs were primarily involved in angiogenesis, cell migration, focal adhesion. Moreover, miR-150-5p was declined in ONFH exosomes and regulated multiple angiogenesis-related pathways. The miR-150-5p-overexpressed BMSC exosomes were successfully obtained and transported miR-150-5p to endothelial cells. Moreover, the miR-150-5p-modified BMSC exosomes promoted the angiogenesis and migration of endothelial cells.Conclusion: Our results elucidate the exosomal miRNA expression profiles in ONFH, and miR-150-5p-modified BMSC exosomes protect against ONFH by promoting angiogenesis, suggesting a new molecular knowledge for the clinical application of ONFH.

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Section: Discussionmentioning

confidence: 99%

MiR-150-5p-modified Bone Marrow Mesenchymal Stem Cells Derived Exosomes Ameliorate Osteonecrosis of Femoral Head by Promoting Endothelial Cell Angiogenesis

Fang¹,

He²,

Jiang³

et al. 2020

Preprint

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“…CCK-8 analysis was conducted to test cell survival/growth as described previously 57 , 58 . Briefly, LO2, bEnd.3, HMECs, and RAW264.7 cells (5 × 10 3 cells/well) were incubated in 96-well culture plates and treated with α-hemolysin (for LO2: 300 ng mL -1 ; for bEnd.3: 1200 ng mL -1 ), F-AgÅPs (for HMECs: 5 ng μL -1 ; for LO2, RAW264.7, and VSMCs: 10 ng μL -1 ; for bEnd.3: 15 ng μL -1 ), α-hemolysin + F-AgÅPs, LPS (100 ng mL -1 ), LPS + F-AgÅPs, vehicle- or F-AgÅPs-pretreated α-hemolysin (for LO2: 300 ng mL -1 ; for bEnd.3: 1200 ng mL -1 ), α-hemolysin-reduced supernatant, or an equal volume of vehicle (normal saline or PBS + normal saline) for 24 h, followed by incubation for another 3 h in fresh medium containing CCK-8 reagent (10 μL per well; 7Sea Biotech, Shanghai, China).…”

Section: Methodsmentioning

confidence: 99%

Fructose-coated Ångstrom silver prevents sepsis by killing bacteria and attenuating bacterial toxin-induced injuries

Yin¹,

Zhou²,

Chen³

et al. 2021

Theranostics

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Serious infection caused by multi-drug-resistant bacteria is a major threat to human health. Bacteria can invade the host tissue and produce various toxins to damage or kill host cells, which may induce life-threatening sepsis. Here, we aimed to explore whether fructose-coated Ångstrom-scale silver particles (F-AgÅPs), which were prepared by our self-developed evaporation-condensation system and optimized coating approach, could kill bacteria and sequester bacterial toxins to attenuate fatal bacterial infections. Methods: A series of in vitro assays were conducted to test the anti-bacterial efficacy of F-AgÅPs, and to investigate whether F-AgÅPs could protect against multi-drug resistant Staphylococcus aureus ( S. aureus )- and Escherichia coli ( E. coli )-induced cell death, and suppress their toxins ( S. aureus hemolysin and E. coli lipopolysaccharide)-induced cell injury or inflammation. The mouse models of cecal ligation and puncture (CLP)- or E. coli bloodstream infection-induced lethal sepsis were established to assess whether the intravenous administration of F-AgÅPs could decrease bacterial burden, inhibit inflammation, and improve the survival rates of mice. The levels of silver in urine and feces of mice were examined to evaluate the excretion of F-AgÅPs. Results: F-AgÅPs efficiently killed various bacteria that can cause lethal infections and also competed with host cells to bind with S. aureus α-hemolysin, thus blocking its cytotoxic activity. F-AgÅPs inhibited E. coli lipopolysaccharide-induced endothelial injury and macrophage inflammation, but not by directly binding to lipopolysaccharide. F-AgÅPs potently reduced bacterial burden, reversed dysregulated inflammation, and enhanced survival in mice with CLP- or E. coli bloodstream infection-induced sepsis, either alone or combined with antibiotic therapy. After three times injections within 48 h, 79.18% of F-AgÅPs were excreted via feces at the end of the 14-day observation period. Conclusion: This study suggests the prospect of F-AgÅPs as a promising intravenous agent for treating severe bacterial infections.

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“…As adult stem cells, USCs are believed to have potential in regenerative medicine in addition to urological applications. Other potential application areas may include stress urinary incontinence [ 31 , 32 ], erectile dysfunction [ 18 , 33 ], acute kidney injury [ 24 , 34 ], chronic kidney disease [ 35 ], vascular diseases [ 22 ], diabetes mellitus [ 36 , 37 ], diabetic nephropathy [ 38 , 39 ], chronic liver injury [ 40 ], inflammatory bowel diseases [ 41 ], neuron regeneration [ 42 ], osteonecrosis of the femoral head [ 43 ], bone [ 44 , 45 ] and cartilage regeneration [ 46 ], and skin wounds healing [ 47 ]. Induced pluripotent stem cells generated from urine-derived cells or USCs can further expand the application areas [ 48 ], such as in cardiac repair [ 49 ], dental reconstruction [ 50 ], disease modeling and drug screening [ 51–57 ].…”

Section: Reviewmentioning

confidence: 99%

“…Chen et al . showed that the extracellular vesicles secreted by USCs prevented early-stage glucocorticoid-induced osteonecrosis in a rat model, and the underlying mechanism could be the delivery of pro-angiogenic DMBT1 and anti-apoptotic TIMP1 [ 43 ]. Altogether, researchers have paid extensive attention to the effective osteogenic differentiation of USCs that already have great advantages as seed cells.…”

Section: Reviewmentioning

confidence: 99%

Urine-derived stem cells: applications in skin, bone and articular cartilage repair

Zhang

Huang

et al. 2021

Burns &Amp; Trauma

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As an emerging type of adult stem cell featuring non-invasive acquisition, urine-derived stem cells (USCs) have shown great potential for applications in tissue engineering and regenerative medicine. With a growing amount of research on the topic, the effectiveness of USCs in various disease models has been shown and the underlying mechanisms have also been explored, though many aspects still remain unclear. In this review, we aim to provide an up-to-date overview of the biological characteristics of USCs and their applications in skin, bone and articular cartilage repair. In addition to the identification procedure of USCs, we also summarize current knowledge of the underlying repair mechanisms and application modes of USCs. Potential concerns and perspectives have also been summarized.

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Extracellular vesicles from human urine-derived stem cells inhibit glucocorticoid-induced osteonecrosis of the femoral head by transporting and releasing pro-angiogenic DMBT1 and anti-apoptotic TIMP1

Cited by 37 publications

References 53 publications

MiR-150-5p-modified Bone Marrow Mesenchymal Stem Cells Derived Exosomes Ameliorate Osteonecrosis of Femoral Head by Promoting Endothelial Cell Angiogenesis

MiR-150-5p-modified Bone Marrow Mesenchymal Stem Cells Derived Exosomes Ameliorate Osteonecrosis of Femoral Head by Promoting Endothelial Cell Angiogenesis

Fructose-coated Ångstrom silver prevents sepsis by killing bacteria and attenuating bacterial toxin-induced injuries

Urine-derived stem cells: applications in skin, bone and articular cartilage repair

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