Human umbilical cord mesenchymal stem cells derived-exosomes in diseases treatment

Yaghoubi, Yoda; Movassaghpour, Aliakbar; Zamani, Majid; Talebi, Mehdi; Mehdizadeh, Amir; Yousefi, Mehdi

doi:10.1016/j.lfs.2019.116733

Cited by 190 publications

(119 citation statements)

References 94 publications

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“…10,14,15 Among the many subtypes of EVs, exosomes are considered to be powerful cell-to-cell communicationrelevant components of the MSC secretome with low immunogenicity and tumorigenicity. 16,17 Exosomes released from hUMSCs (hUMSC-Exos) are reported to suppress ovarian granulosa cell apoptosis and regulate the immune response. 18,19 These small 40 to 150 nm EVs carrying microRNAs (miRNAs) that regulate gene expression may replace cell-based therapies for POI treatment.…”

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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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%

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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“…In vitro tuber formation assays revealed that USC-Exo could promote the angiogenic activities of HUVEC. The results suggest that protection effects of USC-Exo on enhancing spinal cord neurological functional healing is likely attributable to its stimulatory effects on endothelial angiogenesis.Compare with the BMSCs and umbilical cord MSCs, the application exosome in our study derived from the human urine MSC, which could be obtained through noninvasive approach, maybe the best cell source for exosome extraction, and has beenconsidered a new innovative therapeutic strategy for spinal cord regeneration in translated in clinical setting [21].…”

Section: Discussionmentioning

confidence: 99%

Local delivery of USC-derived Exosome Carrying ANGPTL3 Enhance Spinal Cord Functional Recovery After Injury by Promoting Angiogenesis

Yan

Cao

Chen

et al. 2020

Preprint

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Abstract Background: Spinal cord injury (SCI) is a devastating clinical diseasewithout effectivetherapeuticapproach recently. In this study, we aim to investigate the effect of locally injection with exosome derived human urine stem cell (USC) embedding with hydrogelcould improve the spinal cord functional recovery after injury and the underlying mechanism.Methods:Exosome were isolate from USC andidentified by transmission electron microscopy and western blot. Functional assays using human umbilical vein endothelial cell (HUVEC) in vitro were performed to assess the effects of USC-Exosdeliverythe angiopoietin-like protein 3 (ANGPTL3) on tube formation and migration as well as their regulatory role in the PI3K/AKT signaling pathway activation. In vivo experiment we locally injection with exosome derived USC embedding with hydrogel for treatment of SCI. The effects of USC-Exos on functional recovery in spinal cord injury mice were tested by measuring motor evoked potential, histological and neovascular numbers. Meanwhile, the role of the candidate protein ANGPTL3 in USC-Exo for promoting angiogenesisin SCI was assessed.Results:In current study, we demonstrate that when given locallyinjection with exosomederivedhuman urine stem cell (USC) embeddingwith hydrogelcould pass the spinal cord blood brain barrier and delivery the angiopoietin-like protein 3 (ANGPTL3) to the injured spinal cord region. In addition, the administration of exosome derived from human USC could enhance spinal cord neurological functional recovery by promoting angiogenesis.The mechanism studies revealed that ANGPTL3 are enriched in USCexosome(USC-Exo) and required for USC exosome promoting angiogenesis. Functional studies further confirmed the effects caused by exosome derived from USC on angiogenesis wasmediated by PI3K/AKT signaling pathway. Conclusion:Collectively, our results indicated that USC derived exosome serve as a critical regulator of angiogenesis by transferring ANGPTL3 and may represent a promising novel therapeutic agent for SCI repair.

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“…Previous studies have proved that the exosomes from HucMSCs have therapeutic effects in a variety of diseases, such as immune diseases, Alzheimer's disease, in ammatory bowel disease, spinal cord nerve injury, cancer, and ischemia, which are similar to the therapeutic effects of HucMSCs [5,18]. To further explore the effect of exosomes on osteogenic differentiation, we isolated the exosomes produced by HucMSCs.…”

Section: Expression Of Microrna In Exosomesmentioning

confidence: 99%

“…In addition, MSCs affected by the microenvironment of osteogenic differentiation gradually differentiate into osteoblasts, and the expression of proliferation information is reduced; therefore, the exosomes may lack material information to promote proliferation or regulate other functions. For example, studies have con rmed that HucMSC-derived exosomes have the functions of local regulation of osteogenic differentiation, promotion of cell proliferation, promotion of angiogenesis, and regulation of immune response [5,18].…”

Section: Expression Of Microrna In Exosomesmentioning

confidence: 99%

“…MSC-derived exosomes contain a variety of bioactive substances, and have the functions of low immunogenicity, immune regulation, promoting proliferation, and promoting tissue repair. For example, MSC-derived exosomes have therapeutic effects on diabetes, renal disease, and ischemic stroke [5,6]. MicroRNAs (miRNAs) are one of the main bioactive substances in exosomes, and comprise endogenous non-coding single-stranded small RNAs (18)(19)(20)(21)(22)(23)(24)(25) nucleotides in length) that regulate gene expression at the post-transcriptional level by binding to the 3' untranslated region (UTR) region of target mRNAs [7].…”

Section: Introductionmentioning

confidence: 99%

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The role and mechanism of exosomes from umbilical cord mesenchymal stem cells in inducing osteogenesis and preventing osteoporosis

Wang²

2020

Preprint

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BackgroundMesenchymal stem cell (MSC) exosomes promote tissue regeneration and repair, and thus might be used to treat many diseases; however, the influence of microenvironmental conditions on exosomes remains unclear. The present study aimed to analyze the effect of the osteogenic differentiation microenvironment on the functions of human umbilical cord MSCs (HucMSC)-derived exosomes. We explored the role and mechanism by which exosomes promote osteogenic differentiation and prevent osteoporosis, and propose a method to treat and prevent osteoporosis.MethodsHucMSCs were isolated from human umbilical cords, and after osteogenic differentiation and normal culture for 48 h, cell supernatants were collected to isolate exosomes. Exosomes from standardized stem cell culture (Exo1) and osteogenic differentiation-exosomes (Exo2) were co-cultured with osteoblasts, separately. Cell counting kit-8 assays, and alkaline phosphatase and alizarin red staining were used to observe the exosomes’ effects on osteoblast proliferation and differentiation. The levels of osteogenic differentiation-related proteins were analyzed using western blotting. Estrogen-deficient osteoporosis model mice were established, and treated with the two exosomes preparations. Micro-computed tomography and hematoxylin and eosin staining were performed after 6 weeks. MicroRNAs in Exo1 and Exo2 were sequenced and analyzed using bioinformatics.ResultsTreatment with Exo1 and Exo2 enhanced osteoblast osteogenic differentiation significantly, and osteogenic differentiation-related gene and protein expression increased significantly in a concentration-dependent manner. Compared with Exo1 group, Exo2 had a stronger osteogenic differentiation promoting effect, but a weaker proliferation promoting effect. Exo1 and Exo2 significantly improved the tibial density of osteoporosis model mice, with no significant differences between the groups. Sequencing and bioinformatics analysis showed that hsa-mir-328-3p and hsa-mir-2110 might be exosome osteogenesis regulatory microRNAs. Compared with Exo1, the target genes of Exo2-carried microRNAs are enriched in osteoclast differentiation and PPAR signaling. ConclusionsHucMSC-derived exosomes can promote osteogenic differentiation. Exosomes produced in an osteogenic differentiation microenvironment had a stronger osteogenic function, but a weaker proliferative effect. HucMSC-derived exosomes have a therapeutic effect on osteoporosis. The exosomes induced by osteoblasts carry microRNAs that regulate osteoblast differentiation, which might function via osteoblast, adipocyte, and osteoclast differentiation signaling pathways.

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Human umbilical cord mesenchymal stem cells derived-exosomes in diseases treatment

Cited by 190 publications

References 94 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

Local delivery of USC-derived Exosome Carrying ANGPTL3 Enhance Spinal Cord Functional Recovery After Injury by Promoting Angiogenesis

The role and mechanism of exosomes from umbilical cord mesenchymal stem cells in inducing osteogenesis and preventing osteoporosis

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