1489 Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Accelerate Growth of VK2 Vaginal Epithelial Cells through Micrornas In Vitro

Zhu, Zhiling; Wu, Lijun; Ding, Jianxun; Hua, K

doi:10.1016/j.jmig.2019.09.285

Cited by 8 publications

(13 citation statements)

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“…20 In addition, the hUMSC-derived exosomal miRNAs miR-100 and miR-146a can accelerate vaginal epithelial cell proliferation. 21 Moreover, miRNAs including miR-93, miR-34a, miR-214, and miR-217 have been reported to control reactive oxygen species (ROS) levels in OS-driven aging diseases. 22 Nevertheless, the miRNA expression profile of hUMSC-Exos and the downstream target mRNAs have never been investigated.…”

Section: Introductionmentioning

confidence: 99%

“…An exosomal miRNA (miR‐10a) from amniotic fluid stem cells has been reported to rescue cyclophosphamide (CTX)‐induced POF 20 . In addition, the hUMSC‐derived exosomal miRNAs miR‐100 and miR‐146a can accelerate vaginal epithelial cell proliferation 21 . Moreover, miRNAs including miR‐93, miR‐34a, miR‐214, and miR‐217 have been reported to control reactive oxygen species (ROS) levels in OS‐driven aging diseases 22 .…”

Section: Introductionmentioning

confidence: 99%

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Exosomal miRNA-17-5p derived from human umbilical cord mesenchymal stem cells improves ovarian function in premature ovarian insufficiency by regulating SIRT7

et al. 2020

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Premature ovarian insufficiency (POI) is clinically irreversible in women aged over 40 years. Although numerous studies have demonstrated satisfactory outcomes of mesenchymal stem cell therapy, the underlying therapeutic mechanism remains unclear. Exosomes were collected from the culture medium of human umbilical cord mesenchymal stem cells (hUMSCs) and assessed by electron microscopy and Western blot (WB) analysis. Then, exosomes were added to the culture medium of cyclophosphamide (CTX)‐damaged human granulosa cells (hGCs), and the mixture was injected into the ovaries of CTX‐induced POI model mice before detection of antiapoptotic and apoptotic gene expression. Next, the microRNA expression profiles of hUMSC‐derived exosomes (hUMSC‐Exos) were detected by small RNA sequencing. The ameliorative effect of exosomal microRNA‐17‐5P (miR‐17‐5P) was demonstrated by miR‐17‐5P knockdown before assessment of ovarian phenotype and function, reactive oxygen species (ROS) levels and SIRT7 expression. Finally, SIRT7 was inhibited or overexpressed by RNA interference or retrovirus transduction, and the protein expression of PARP1, γH2AX, and XRCC6 was analyzed. The ameliorative effect of hUMSC‐Exos on POI was validated. Our results illustrated that hUMSC‐Exos restored ovarian phenotype and function in a POI mouse model, promoted proliferation of CTX‐damaged hGCs and ovarian cells, and alleviated ROS accumulation by delivering exosomal miR‐17‐5P and inhibiting SIRT7 expression. Moreover, our findings elucidated that miR‐17‐5P repressed PARP1, γH2AX, and XRCC6 by inhibiting SIRT7. Our findings suggest a critical role for exosomal miR‐17‐5P and its downstream target mRNA SIRT7 in hUMSC transplantation therapy. This study indicates the promise of exosome‐based therapy for POI treatment.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Exosomal miRNA-17-5p derived from human umbilical cord mesenchymal stem cells improves ovarian function in premature ovarian insufficiency by regulating SIRT7

et al. 2020

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“…Unfortunately, tendon injury is difficult to fully recover from and is often accompanied by a fibrotic healing process characterized by the initial inflammatory responses and subsequent myofibroblast activation and collagen deposition, causing tendon adhesion with the peritendinous tissues [26,27], which, given the lack of preventive methods, can require a second myotenolysis surgery. As ideal effector molecule carriers and biocompatible therapeutic tools with pure biogenic derivation, EVs are becoming rising stars in treating illness, showing pleiotropic function and prompting encouraging results in various organs and systems [28][29][30]. Tendon repair has already been found to be promoted by EVs from BMSCs and ADSCs [9,10,31].…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles from hydroxycamptothecin primed umbilical cord stem cells enhance anti-adhesion potential for treatment of tendon injury

Yao

Xiong

et al. 2020

Stem Cell Res Ther

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Background Peritendinous fibrosis represents a fibrotic healing process that usually occurs after tendon injury or surgery. This worldwide challenge hampers the functional rehabilitation and the mobility of extremities. However, effective treatment is still lacking at present. The aim of our study was to explore the effect of extracellular vesicles derived from hydroxycamptothecin primed human umbilical cord stem cells (HCPT-EVs) on post-traumatic tendon adhesion. Methods Extracellular vesicles derived from unprimed human umbilical cord mesenchymal stem cells (Unprimed EVs) or HCPT-EVs were isolated and characterized. A rat model of Achilles tendon injury was used to confirm the anti-adhesion effect of HCPT-EVs and compared with that of Unprimed EVs in vivo. In vitro, the inhibitory effects of HCPT-EVs on fibroblast proliferation, viability, and myofibroblast differentiation upon TGF-β1 stimulation were compared with the effects of Unprimed EVs. For mechanistic analysis, the expression of endoplasmic reticulum stress (ERS)-associated proteins was examined among the effector cargos of HCPT-EVs and Unprimed EVs. The ERS antagonist salubrinal was used to determine the ERS dependence of the anti-adhesion effects of HCPT-EVs. Results There were no obvious differences between Unprimed EVs and HCPT-EVs in terms of morphology, particle size, characteristic protein expression, and cellular uptake. HCPT-EVs exhibited a fortified anti-adhesion effect after Achilles tendon injury compared with Unprimed EVs. Fibroblast proliferation and viability and myofibroblast differentiation were all inhibited by HCPT-EVs. These properties were superior for HCPT-EVs relative to Unprimed EVs. Mechanistically, HCPT-EVs contained more ERS-associated protein than Unprimed EVs and activated the ERS pathway in fibroblast to counteract myofibroblast differentiation. Conclusion This study demonstrates that HCPT-EVs show high anti-adhesion potential for the treatment of tendon injury by provoking ERS in fibroblasts. HCPT-EVs represent a promising strategy for clinical use in treating adhesion-related diseases.

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“…As miRNAs are abundant in HUMSC-derived exosomes, we hypothesized that HUMSC-exosomes promote the healing of corneal epithelial defect mainly through miRNAs. The downloaded dataset was used to determine the content of various miRNAs in HUMSC-exosomes [21]. Among the several miRNAs selectively enriched in HUMSC-exosomes, we focused on the most abundant one, miR-21(Fig.…”

Section: Humsc-exosomes Promote Hcecs Proliferation and Migration Through Mir-21mentioning

confidence: 99%

Umbilical Cord Mesenchymal Stem Cells-derived Exosomes Deliver Mir-21 to Accelerate Corneal Epithelial Wound Healing Through PTEN/PI3K/Akt pathway

Li¹,

Liu²,

Zhang³

et al. 2021

Preprint

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BackgroundRapid restoration of corneal epithelium integrity after injury is particularly important for preserving corneal transparency and vision. Mesenchymal stem cells (MSCs) can be taken into account as the promising regenerative therapeutics for improvement of wound healing processes based on the variety of the effective components. The extracellular vesicles form MSCs, especially exosomes, has been considered as important paracrine mediators though transferring microRNAs into recipient cell. This study investigated the mechanism of human umbilical cord MSC-derived exosomes (HUMSC-exosomes) on corneal epithelial wound healing.MethodsExosomes extracted from HUMSCs were identified by transmission electron microscopy, nanoparticle tracking analysis, and Western blot. Corneal fluorescein staining and histological staining were evaluated in a corneal mechanical wound model. Changes in HCECs proliferation after HUMSC-exosomes or miR-21 mimic treatment were evaluated by CCK-8 and EdU assays, while migration was assessed by in vitro scratch wound assay. Full-length transcriptome sequencing was performed to identify the differentially expressed genes associated with HUMSC-exosomes treatment, followed by validation via real-time PCR and Western blot.ResultsThe exosomes derived from HUMSCs can significantly promote corneal epithelial cells proliferation, migration in vitro and accelerate corneal epithelial wound healing in vivo. Similar effects were obtained after miR-21 transfection, while the beneficial effects of HUMSC-exosomes were partially negated by miR-21 knockdown. Results also show that the benefits are associated with decreased PTEN level and activated the PI3K/Akt signaling pathway in HCECs.ConclusionsHUMSC-exosomes could accelerate the recovery of corneal epithelial wounds though restraining PTEN by transferring miR-21, and may represent a promising novel therapeutic agent for corneal wound repair.

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1489 Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells Accelerate Growth of VK2 Vaginal Epithelial Cells through Micrornas In Vitro

Cited by 8 publications

References 0 publications

Exosomal miRNA-17-5p derived from human umbilical cord mesenchymal stem cells improves ovarian function in premature ovarian insufficiency by regulating SIRT7

Exosomal miRNA-17-5p derived from human umbilical cord mesenchymal stem cells improves ovarian function in premature ovarian insufficiency by regulating SIRT7

Extracellular vesicles from hydroxycamptothecin primed umbilical cord stem cells enhance anti-adhesion potential for treatment of tendon injury

Umbilical Cord Mesenchymal Stem Cells-derived Exosomes Deliver Mir-21 to Accelerate Corneal Epithelial Wound Healing Through PTEN/PI3K/Akt pathway

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