ACTA BIOCHIMICA ET BIOPHYSICA SINICA
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2022
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IF 3.511
Qinghui Han,Shuguang Wang,Dawei Chen,Di Gan,Tao Wang
Tendon injuries are common clinical issues resulted from tissue overuse and age-related degeneration. Previous sutdies have suggested that exosomes secreted by mesenchymal stem cells (MSCs) contribute to tissue injury repair. Here, we provide evidence for a critical role of human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes in reducing tendon injury by activating the RhoA signaling. Treatment of primary injured tenocytes with hucMSC exosomes increases cell proliferation and invasion, which correlates with increased RhoA activity. RhoA mediates the effects of hucMSC exosomes, as treatment of primary injured tenocytes with the RhoA inhibitor, CCG-1423, abolishes the effects of hucMSC exosomes on cell proliferation and invasion. Mechanistically, we observe that hucMSC exosomes induce the expression of a microRNA, miR-27b-3p, which targets and suppresses ARHGAP5, a negative regulator of RhoA. Consistent with this observation, ARHGAP5 overexpression suppresses the effects of hucMSC exosomes on cell proliferation and invasion, while knockdown of ARHGAP5 rescues these effects. Finally, we demonstrate the functional significance of our findings in vivo using an Achilles tendon injury model and show that treatment with exosomes reduces tendon injury in rats, which correlates with increased RhoA activity and reduced ARHGAP5 expression. Taken together, our findings highlight a critical role of hucMSC exosomes in reducing tendon injury via miR-27b-3p-mediated suppression of ARHGAP5, resulting in RhoA activation, and leading to increased cell proliferation and invasion of primary injured tenocytes.
研究领域:
干细胞生物学
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分子生物学
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再生医学
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骨科
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DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
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2025
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IF 8.5
Yuhui Yang,Yong He,Hui Xing,Ziyi Zhao,Jianjin Wang,Shanying Li,Xiaosong Xu,Dong Ma,Yunfeng Hu
Long-term exposure to ultraviolet (UV) radiation can damage human skin, resulting in photodamage. Repairing photodamaged skin has been a major focus of research in recent years. Extensive research has shown that human umbilical cord mesenchymal stem cell-derived exosomes (Exo) possess anti-inflammatory, pro-angiogenic, and wound healing properties, holding great potential for treating skin damage. However, due to the limitations of exosomes alone, such as poor transdermal penetration, instability, and low utilization, there is an urgent need for new delivery strategies. We designed a hybrid nanovesicle (HL@Exo) by combining ultrasonic incubation with membrane extrusion to fuse Exo with HL. HL@Exo capitalizes on the advantages of liposomal carriers and the permeation-enhancing properties of hyaluronic acid to effectively facilitate transdermal delivery of Exo. The successful fusion of HL@Exo and its skin penetration were verified by methods such as fluorescent labeling, western blotting, Transwell assays, and in vivo imaging. In vitro studies on photodamaged keratinocytes and endothelial cells demonstrated HL@Exo ability to promote cell proliferation, repair, angiogenesis, and reduce inflammation. In a laser-induced skin photodamage model, HL@Exo enhanced collagen regeneration, accelerated wound healing, and demonstrated significant anti-inflammatory effects, indicating its potential as a non-invasive treatment and offering a novel strategy for the clinical application of Exo.
研究领域:
生物学
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医学
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药剂学
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产品关联
DOI
PubMed
高影响因子
Stem Cells International
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2025
·Vol. 2025
·期 1
·5243270
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IF 3.3
Bei Li,Qiongni Wang,Linru Shi,Qifeng Liu,Hui Qian,Lixia Yu,Cheng Ji
Diabetic kidney disease (DKD) is characterized by a continuous decline in renal function and progressive fibrosis, making it a leading cause of end-stage kidney disease with limited therapeutic options. Recently, extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have shown great potential in tissue regeneration and repair, offering a new avenue for the treatment of DKD. The purpose of this study is to explore the function and mechanism of action of EVs derived from human umbilical cord MSCs (hucMSC-EVs) in the development of DKD. Our findings show that under high-glucose (HG) conditions, miR-146b-5p is highly expressed in glomerular mesangial cells, downregulating the target protein Merlin, which promotes the activation of the YAP signaling pathway and induces mesangial cell fibrotic-like changes, leading to a significant deposition of collagen and interstitial fibrosis in the kidney. In vivo and in vitro experimental findings reveal that hucMSC-EVs can significantly inhibit miR-146b-5p, upregulate Merlin expression, prevent the nuclear translocation of YAP, improve renal function, and reduce collagen deposition, demonstrating a significant antifibrotic effect. The findings of this study emphasize the central role of the miR-146b-5p/Merlin/YAP axis in hucMSC-EVs-mediated inhibition of renal fibrosis and highlight the potential of MSC-EVs as a targeted nanotherapeutic strategy for DKD.
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产品关联
DOI
PubMed
高影响因子
CARBOHYDRATE POLYMERS
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2025
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IF 12.5
Qiuxia Zheng,Jia Yao,Zongbin Sun,Rui Li,Yue Zhang,Pan Jiang,Ye Xie,Xiaojing Song,Hongfa Sun,Dan Zhu,Haixu Ni,Xun Li
Hepatectomy is the primary therapeutic intervention for liver disorders. Nonetheless, an increased risk of liver failure and postoperative mortality exists due to the rapid reduction in liver size after surgery. Human umbilical cord mesenchymal stem cell (hucMSC) exosomes (Exos) have been recognized in the promotion of liver regeneration. However, intravenous administration of Exos faces several challenges including poor targeting and rapid clearance. Herein, we employed CMCS/OHA/LA-loaded hucMSCs derived Exos (hydrogel-Exos) to address liver regeneration after hepatectomy. Release and uptake studies showed hydrogel-Exos enables localized release of Exos, prolonging their presence and concentration in liver tissue. Meanwhile, the hydrogel-Exos exhibited good characteristics in injectability, self-healing, biocompatibility, liver adhesion, swelling performance, postoperative hemostasis and minimization of peritoneal adhesions post-resection. Moreover, proliferation and scratch wound healing assays demonstrated the ability of hydrogel-Exos to promote liver cell proliferation and migration. During in vivo studies, the Exos-containing hydrogel was injected into the resected surface of a 70 % hepatectomy rat model. The result indicated Exos was released into the liver tissue through the hydrogel to promote angiogenesis and liver regeneration. Bioinformatics analysis revealed liver regeneration mechanisms involve cell cycle-related pathways. As such, hydrogel-encapsulated Exos appeared promising to be employed following hepatectomy.
研究领域:
医学
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生物材料学
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再生医学
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产品关联
DOI
PubMed
高影响因子
BIOMATERIALS
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2024
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IF 12.8
YuLing Yang,JiaNi Zhang,SiWen Wu,Yu Deng,ShiHan Wang,Li Xie,XiaoPeng Li,Li Yang
Mesenchymal stem cell (MSC)-based therapy is an effective strategy for regenerative therapy. However, safety and ease of use are still issues to be overcome in clinical applications. Exosomes are naturally derived nanoparticles containing bioactive molecules, which serve as ideal cell-free therapeutic modalities. However, issues such as delivery, long-term preservation and activity maintenance of exosomes are other problems that limit their application. In this study, we proposed the use of rapid freeze-dry-thaw macroporous hydrogels for the encapsulation of HucMSC-derived exosomes (HucMSC-Exos) combined with an antimicrobial peptide coating. This exosome-encapsulated hyaluronic acid macroporous hydrogel HD-DP7/Exo can achieve long-term storage and transport by lyophilization and can be rapidly redissolved for treatment. After comprehensively comparing the therapeutic effects of HucMSC-Exos and HucMSC-loaded hydrogels, we found that HucMSC-Exos could also effectively regulate fibroblasts, vascular endothelial cells, and macrophages and inhibit myofibroblast-mediated fibrosis, thus promoting tissue regeneration and inhibiting scar formation in a mouse model of deep second-degree burn infection healing. These properties of lyophilized storage and whole-process-repair make HD-DP7/Exo have potential application value and application prospects.
研究领域:
再生医学
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组织工程
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伤口愈合
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纳米技术
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生物材料
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产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）