Exosomes derived from human umbilical cord mesenchymal stem cells accelerate growth of VK2 vaginal epithelial cells through MicroRNAsin vitro

Zhu, Zhanping; Zhang, Yijing; Zhang, Yiqun; Zhang, Hongdao; Liu, Wei; Zhang, Ning; Zhang, Xiaodan; Zhou, Guannan; Wu, Ligang; Hua, Keqin; Ding, Jingxin

doi:10.1093/humrep/dey344

Cited by 61 publications

(36 citation statements)

References 29 publications

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“…38 As a novel generation of cell-free nanomaterial, HUMSC-Exos has demonstrated promising efficacy in many areas of tissue repair. The currently proven role of HUMSC-Exos included accelerated skin, 39 vaginal 40 and fracture healing, 41 reduction of type 2 diabetes. 42 It is not difficult to find that HUMSC-Exos promoted tissue repair often associated with inhibition of excessive proliferation of fibrotic tissue.…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-21-3p Engineered Umbilical Cord Stem Cell-Derived Exosomes Inhibit Tendon Adhesion

Yao¹,

Li²,

Wang³

et al. 2020

JIR

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As a common complication of tendon injury, tendon adhesion is an unresolved problem in clinical work. The aim of this study was to investigate whether human umbilical cord mesenchymal stem cell-derived exosomes (HUMSC-Exos), one of the most promising new-generation cell-free therapeutic agents, can improve tendon adhesion and explore potential-related mechanisms. Methods: The rat Achilles tendon injury adhesion model was constructed in vivo, and the localization of HUMSC-Exos was used to evaluate the tendon adhesion. Rat fibroblast cell lines were treated with transforming growth factor β1 (TGF-β1) and/or HUMSC-Exos in vitro, and cell proliferation, apoptosis and gene expression were measured. MicroRNA (miRNA) sequencing and quantitative PCR (qPCR) analysis confirmed differential miRNAs. A specific miRNA antagonist (antagomir-21a-5p) was used to transform HUMSC-Exos and obtain modified exosomes to verify its efficacy and related mechanism of action. Results: In this study, we found HUMSC-Exos reduced rat fibroblast proliferation and inhibited the expression of fibrosis genes: collagen III (COL III) and α-smooth muscle actin (α-SMA) in vitro. In the rat tendon adhesion model, topical application of HUMSC-Exos contributed to relief of tendon adhesion. Specifically, the fibrosis and inflammationrelated genes were simultaneously inhibited by HUMSC-Exos. Further, miRNA sequencing of HUMSCs and HUMSC-Exos showed that miR-21a-3p was expressed at low abundance in HUMSC-Exos. The antagonist targeting miR-21a-3p was recruited for treatment of HUMSCs, and harvested HUMSC-Exos, which expressed low levels of miR-21a-3p, and expanded the inhibition of tendon adhesion in subsequent in vitro experiments. Conclusion: Our results indicate that HUMSC-Exos may manipulate p65 activity by delivering low-abundance miR-21a-3p, ultimately inhibiting tendon adhesion. The findings may be promising for dealing with tendon adhesion.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-21-3p Engineered Umbilical Cord Stem Cell-Derived Exosomes Inhibit Tendon Adhesion

Yao¹,

Li²,

Wang³

et al. 2020

JIR

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“…A previous study showed that human umbilical cord mesenchymal stem cell-derived exosomes could be internalized by vaginal epithelial cells. 21 Moreover, BMSC-exos can be taken up by adipocytes, myocytes, and hepatocytes. 22 In our study, spermatogonia (GC1-spg cells) showed uptake of BMSC-exos efficiently, consistent with previous research.…”

Section: Discussionmentioning

confidence: 99%

Protective effect of bone marrow mesenchymal stem cell-derived exosomes against the reproductive toxicity of cyclophosphamide is associated with the p38MAPK/ERK and AKT signaling pathways

Guo

Zhai

Xia

et al. 2021

Asian Journal of Andrology

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Spermatogenic dysfunction caused by cyclophosphamide (CP) chemotherapy has seriously influenced the life quality of patients. Unfortunately, treatments for CP-induced testicular spermatogenic dysfunction are limited, and the molecular mechanisms are not fully understood. For the first time, here, we explored the effects of bone marrow mesenchymal stem cell-derived exosomes (BMSC-exos) on CP-induced testicular spermatogenic dysfunction in vitro and in vivo . BMSC-exos could be taken up by spermatogonia (GC1-spg cells). CP-injured GC1-spg cells and BMSC-exos were cocultured at various doses, and then, cell proliferation was measured using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. In addition, photophosphorylation of extracellular-regulated kinase (ERK), p38 mitogen-activated protein kinase (p38MAPK), and protein kinase B (AKT) proteins was evaluated by western blotting as well as apoptosis in GC1-spg cells measured using flow cytometry. Treatment with BMSC-exos enhanced cell proliferation and reduced apoptosis of CP-injured GCI-spg cells. Phosphorylated levels of ERK, AKT, and p38MAPK proteins were reduced in CP-injured spermatogonia when co-treated with BMSC-exos, indicating that BMSC-exos acted against the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways. In experiments in vivo , CP-treated rats received BMSC-exos by injection into the tail vein, and testis morphology was compared between treated and control groups. Histology showed that transfusion of BMSC-exos inhibited the pathological changes in CP-injured testes. Thus, BMSC-exos could counteract the reproductive toxicity of CP via the p38MAPK/ERK and AKT signaling pathways. The findings provide a potential treatment for CP-induced male spermatogenic dysfunction using BMSC-exos.

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“…Moreover, exosomes may carry specific cargo such as foreign miRNA products. For example, in a study of MSCs genetically modified to overexpress a variety of miRNAs, including miRNA-100, miRNA-146a, miRNA-21, miRNA221 and miRNA-143, it was found that these exosomes enhance DNA synthesis, thus promoting the proliferation of vaginal epithelial cells [83]. In an acute lung injury model, exosomes from miRNA-30b-3p-overexpressing MSCs protected type II alveolar epithelial cells against apoptosis by downregulating serum amyloid A3 (SAA3) [36].…”

Section: Epithelial Recoverymentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage

Gao

et al. 2020

Cells

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Radiation-induced damage is a common occurrence in cancer patients who undergo radiotherapy. In this setting, radiation-induced damage can be refractory because the regeneration responses of injured tissues or organs are not well stimulated. Mesenchymal stem cells have become ideal candidates for managing radiation-induced damage. Moreover, accumulating evidence suggests that exosomes derived from mesenchymal stem cells have a similar effect on repairing tissue damage mainly because these exosomes carry various bioactive substances, such as miRNAs, proteins and lipids, which can affect immunomodulation, angiogenesis, and cell survival and proliferation. Although the mechanisms by which mesenchymal stem cell-derived exosomes repair radiation damage have not been fully elucidated, we intend to translate their biological features into a radiation damage model and aim to provide new insight into the management of radiation damage.

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Exosomes derived from human umbilical cord mesenchymal stem cells accelerate growth of VK2 vaginal epithelial cells through MicroRNAsin vitro

Cited by 61 publications

References 29 publications

<p>MicroRNA-21-3p Engineered Umbilical Cord Stem Cell-Derived Exosomes Inhibit Tendon Adhesion</p>

<p>MicroRNA-21-3p Engineered Umbilical Cord Stem Cell-Derived Exosomes Inhibit Tendon Adhesion</p>

Protective effect of bone marrow mesenchymal stem cell-derived exosomes against the reproductive toxicity of cyclophosphamide is associated with the p38MAPK/ERK and AKT signaling pathways

Mesenchymal Stem Cell-Derived Exosomes: Biological Function and Their Therapeutic Potential in Radiation Damage

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