Mesenchymal stem cell-derived extracellular vesicles as a new therapeutic strategy for ocular diseases

Yu, Bo; Li, Xiaorong; Zhang, Xiao Min

doi:10.4252/wjsc.v12.i3.178

Cited by 44 publications

(41 citation statements)

References 80 publications

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“…In a murine oxygen-induced retinopathy model, intravitreal injection of MSC-derived EVs reduced the severity of retinal ischemia [18]. Along with in vivo study, in vitro experiment was performed so that pretreatment with EVs could defend R28 cells against oxygen deficiency situations [30]. So far, R28 cells provide an important experimental system for the various studies of retinal ganglion cells, such as retinal cell differentiation, neuroprotection, and neuronal function [23,31].…”

Section: Discussionmentioning

confidence: 99%

UBA2 activates Wnt/β-catenin signaling pathway during protection of R28 retinal precursor cells from hypoxia by extracellular vesicles derived from placental mesenchymal stem cells

et al. 2020

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Background Stem cell transplantation has been proposed as an alternative treatment for intractable optic nerve disorders characterized by irrecoverable loss of cells. Mesenchymal stem cells, with varying tissue regeneration and recovery capabilities, are being considered for potential cell therapies. To overcome the limitations of cell therapy, we isolated exosomes from human placenta-derived mesenchymal stem cells (hPMSCs) and investigated their therapeutic effects in R28 cells (retinal precursor cells) exposed to CoCl2. Method After 9 h of exposure to CoCl2, the hypoxic damaged R28 cells were divided into the non-treatment group (CoCl2 + R28 cells) and treatment group (CoCl2 + R28 cells treated with exosome). Immunoblot analysis was performed for Pcna, Hif-1α, Vegf, Vimentin, Thy-1, Gap43, Ermn, Neuroflament, Wnt3a, β-catenin, phospo-GSK3β, Lef-1, UBA2, Skp1, βTrcp, and ubiquitin. The proteomes of each group were analyzed by liquid chromatography/tandem mass (LC-MS/MS) spectrometry. Differentially expressed proteins (DEPs) were detected by label-free quantification, and the interactions of the proteins were examined through signal transduction pathway and gene ontology analysis. Result We observed that exosome could significantly recover proliferation damaged by CoCl2 treatment. In addition, the treatment group presented the decreased expression of Hif-1α protein (P < 0.05) and increased expression of proliferation marker, Pcna, and nerve regeneration-related factors such as Vimentin, Thy-1, and Neuroflament (P < 0.05) compared with the non-treatment group. In total, 200 DEPs were identified in the non-treatment group and treatment group (fold change ≥ 2, p < 0.05). Catenin and ubiquitin systems (UBA2, UBE2E3, UBE2I) were found in both the DEP lists of downregulated proteins from the non-treatment group and upregulated proteins from the treatment group. The mRNA expressions of ubiquitin systems were significantly decreased under hypoxic conditions. Moreover, UBA2 and Wnt/β-catenin protein were associated with the rescue of the hypoxic damaged R28 cells. Using a siRNA system, we could find it out that hPMSC exosomes could not repair altered expressions of target proteins by CoCl2 in lacking UBA2 R28 cells. Conclusion This study reported that hypoxic damaged expression of regeneration markers in R28 cells was significantly recovered by hPMSC exosomes. We could also demonstrate that UBA2 played a key role in activating the Wnt/β-catenin signaling pathway during protection of hypoxic damaged R28 cells, induced by hPMSC exosomes.

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Section: Discussionmentioning

confidence: 99%

UBA2 activates Wnt/β-catenin signaling pathway during protection of R28 retinal precursor cells from hypoxia by extracellular vesicles derived from placental mesenchymal stem cells

et al. 2020

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“…Exosome biology in the visual system is not well-characterized; recent studies used exosomes mostly to detect and monitor ON trauma and disease [25]. Exosomes derived from photoreceptors are highly expressed in patients after rhegmatogenous retinal detachment [28], and exosomes containing speci c subsets of miRNAs can serve as biomarkers for glaucoma detection and analysis [29].…”

Section: Discussionmentioning

confidence: 99%

UBA2 Activates Wnt/ β-catenin Signaling Pathway during Protection of R28 Retinal Precursor Cells from Hypoxia by Extracellular Vesicles derived from Placental Mesenchymal Stem Cells

Koh

Park

Bae

et al. 2020

Preprint

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Background: Stem cell transplantation has been proposed as an alternative treatment for intractable optic nerve disorders characterized by irrecoverable loss of cells. Mesenchymal stem cells, with varying tissue regeneration and recovery capabilities, are being considered for potential cell therapies. To overcome the limitations of cell therapy, we isolated exosomes from human placenta–derived mesenchymal stem cells (hPMSCs), and investigated their therapeutic effects in R28 cells (retinal precursor cells) exposed to CoCl2. Method: After nine hours of exposure to CoCl2, the hypoxic damaged R28 cells were divided into non treatment group (CoCl2+R28 cells) and treatment group (CoCl2+R28 cells treated with exosome). Immunoblot analysis was performed for Pcna, Hif-1α, Vegf, Vimentin, Thy-1, Gap43, Ermn, Neuroflament, Wnt3a, β-catenin, phospo-GSK3β, Lef-1, UBA2, Skp1, βTrcp, and ubiquitin. The proteomes of each group were analyzed by liquid chromatography/tandem mass (LC-MS/MS) spectrometry. Differentially expressed proteins (DEPs) were detected by label-free quantification and the interactions of the proteins were examined through signal transduction pathway and gene ontology analysis. Result: We observed that Exosome could significantly recover proliferation damaged by CoCl2 treatment. In addition, treatment group presented the decreased expression of Hif-1α protein (P < 0.05) and increased expression of proliferation marker, Pcna, and nerve regeneration–related factors such as Vimentin, Thy-1 and Neuroflament (P < 0.05) compared with non-treatment group. In total, 200 DEPs were identified in non-treatment group and treatment group (fold change ≥ 2, p < 0.05). Catenin and ubiquitin systems (UBA2, UBE2E3, UBE2I) were found in both the DEP lists of downregulated proteins from non-treatment group and upregulated proteins from treatment group. The mRNA expressions of ubiquitin systems were significantly decreased under hypoxic condition. Moreover, UBA2 and Wnt/β-catenin protein were associated with rescue of the hypoxic damaged R28 cells. Using a siRNA system, we could find it out that hPMSC exosoms could not repair altered expressions of target proteins by CoCl2 in lacking UBA2 R28 cells. Conclusion: This study reported that hypoxic damaged expression of regeneration markers in R28 cells were significantly recovered by hPMSC exosomes. We could also demonstrate that UBA2 played a key role in activating the Wnt/β-catenin signaling pathway during protection of hypoxic damaged R28 cells, induced by hPMSC exosomes.

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“…Functionally, MSC-derived EVs containing miRNA-126 play an essential role in reversing the actions of inflammation through the inhibition of high mobility group box 1 (HMGB1). Furthermore, the author found EVs derived from miRNA-126-overexpressed MSCs were more effective in reducing inflammation in diabetic retinopathy [ 99 ].…”

Section: Ev As Therapeutic Tools For Diabetes and Diabetic Complicmentioning

confidence: 99%

Therapeutic Potentials of Extracellular Vesicles for the Treatment of Diabetes and Diabetic Complications

Song

et al. 2020

IJMS

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Extracellular vesicles (EVs), including exosomes and microvesicles, are nano-to-micrometer vesicles released from nearly all cellular types. EVs comprise a mixture of bioactive molecules (e.g., mRNAs, miRNAs, lipids, and proteins) that can be transported to the targeted cells/tissues via the blood or lymph circulation. Recently, EVs have received increased attention, owing to their emerging roles in cell-to-cell communication, or as biomarkers with the therapeutic potential to replace cell-based therapy. Diabetes comprises a group of metabolic disorders characterized by hyperglycemia that cause the development of life-threatening complications. The impacts of conventional clinical treatment are generally limited and are followed by many side effects, including hypoglycemia, obesity, and damage to the liver and kidney. Recently, several studies have shown that EVs released by stem cells and immune cells can regulate gene expression in the recipient cells, thus providing a strategy to treat diabetes and its complications. In this review, we summarize the results from currently available studies, demonstrating the therapeutic potentials of EVs in diabetes and diabetic complications. Additionally, we highlight recommendations for future research.

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Mesenchymal stem cell-derived extracellular vesicles as a new therapeutic strategy for ocular diseases

Cited by 44 publications

References 80 publications

UBA2 activates Wnt/β-catenin signaling pathway during protection of R28 retinal precursor cells from hypoxia by extracellular vesicles derived from placental mesenchymal stem cells

UBA2 activates Wnt/β-catenin signaling pathway during protection of R28 retinal precursor cells from hypoxia by extracellular vesicles derived from placental mesenchymal stem cells

UBA2 Activates Wnt/ β-catenin Signaling Pathway during Protection of R28 Retinal Precursor Cells from Hypoxia by Extracellular Vesicles derived from Placental Mesenchymal Stem Cells

Therapeutic Potentials of Extracellular Vesicles for the Treatment of Diabetes and Diabetic Complications

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