Exosomes Derived From Mesenchymal Stem Cells Modulate miR-126 to Ameliorate Hyperglycemia-Induced Retinal Inflammation Via Targeting HMGB1

Zhang, Wei; Wang, Yan; Kong, Yali

doi:10.1167/iovs.18-25617

Cited by 173 publications

(135 citation statements)

References 35 publications

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“…This finding is further supported by an experiment on MSC‐derived exosomes to examine their influence on hyperglycemia‐induced retinal inflammation. The results indicated that the administration of MSC‐derived exosomes effectively reversed the inflammation induced by hyperglycemia in diabetic rats (Zhang, Wang, & Kong, ). Our data clearly indicate that exosomes derived from osteogenically differentiating MSCs at early stages have an effective inflammation‐regulatory ability.…”

Section: Discussionmentioning

confidence: 99%

Immunoregulatory role of exosomes derived from differentiating mesenchymal stromal cells on inflammation and osteogenesis

Wei

Crawford

et al. 2019

J Tissue Eng Regen Med

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Bone marrow-derived mesenchymal stem/stromal cells (BMSCs) can differentiate into bone-forming osteoblasts, playing a crucial role in bone regeneration. Exosomes are naturally cell-secreted nanovesicles and are lately regraded as an emerging mediator of cellular communication in physiological and pathological conditions. The present study aimed at investigating the complex cellular communications, especially those among the differentiating BMSCs, immune cells (e.g., macrophages), and newly recruited BMSCs via exosome-mediated pathways. Exosomes were first isolated from osteogenically differentiating BMSCs at various stages (Day 0, Day 3, Day 7, and Day 14, respectively). The cellular uptake of isolated exosomes was examined in macrophages and human BMSCs (hBMSCs). The exosomes collected at various osteogenic differentiation stages (0d-exo, 3d-exo, 7d-exo, and 14d-exo) had no effect on the viability of hBMSCs. The uptake of exosomes (0d-exo, 3d-exo, and 7d-exo) significantly decreased proinflammatory-gene expression and the level of an M1 phenotypic marker. Our results then revealed that 3d-exo, 7d-exo, and 14d-exo led to a remarkable increase in mesenchymal stem/stromal cell migration. In addition, 0d-exo significantly promoted the expression of early osteogenic markers, such as alkaline phosphatase and bone morphogenetic protein 2, indicating a pro-osteogenic role of hBMSC-derived exosomes. Collectively, these results suggest that exosomes derived from differentiating mesenchymal stem/stromal cells play a unique osteoimmunomodulatory role in the regulation of bone dynamics.

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Section: Discussionmentioning

confidence: 99%

Immunoregulatory role of exosomes derived from differentiating mesenchymal stromal cells on inflammation and osteogenesis

Wei

Crawford

et al. 2019

J Tissue Eng Regen Med

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“…Furthermore, in human retinal endothelial cells treated with high glucose, HMGB1siRNA reduced oxidative stress and cellular apoptosis. In addition, a recent study demonstrated that exosomes derived from mesenchymal stem cells overexpressing miRNA-126, an endothelial specific miRNA that mediates inflammation, suppressed HMGB1 expression and NF-kB and NLRP3 inflammasome activity in human retinal endothelial cells [136,137]. Finally, protein kinase A (PKA) seems to inhibit cytoplasmic HMGB1 [137].…”

Section: Hmgb1 and Diabetic Retinopathymentioning

confidence: 99%

High Mobility Group Box-1 and Diabetes Mellitus Complications: State of the Art and Future Perspectives

Biscetti

Rando

Nardella

et al. 2019

IJMS

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Diabetes mellitus (DM) is an endemic disease, with growing health and social costs. The complications of diabetes can affect potentially all parts of the human body, from the heart to the kidneys, peripheral and central nervous system, and the vascular bed. Although many mechanisms have been studied, not all players responsible for these complications have been defined yet. High Mobility Group Box-1 (HMGB1) is a non-histone nuclear protein that has been implicated in many pathological processes, from sepsis to ischemia. The purpose of this review is to take stock of all the most recent data available on the role of HMGB1 in the complications of DM.

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“…They found that the implanted MSC-Exo efficiently delivered miRNA-222 into the retina to prevent the progression of retinal degeneration 122 . Similarly, Zhang et al discovered that human umbilical cord MSC-Exo reduces hyperglycaemia-induced retinal inflammation after intravitreal injection into rabbis with DM 123 . Based on the high efficacy of MSC-Exo for RD control in preclinical trials, a clinical trial intending to evaluate the function of serum exosomal miRNA in the pathogenesis of DR has obtained FDA approval (NCT03264976) and will soon recruit patients 124 .…”

Section: Stem Cell-derived Exosomes For Rd Treatmentmentioning

confidence: 94%

Stem/progenitor cell-based transplantation for retinal degeneration: a review of clinical trials

Wang

Tang

2020

Cell Death Dis

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Retinal degeneration (RD) is one of the dominant causes of irreversible vision impairment and blindness worldwide. However, the current effective therapeutics for RD in the ophthalmologic clinic are unclear and controversial. In recent years, extensively investigated stem/progenitor cells—including retinal progenitor cells (RPCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs) and mesenchymal stromal cells (MSCs)—with proliferation and multidirectional differentiation potential have presented opportunities to revolutionise the ultimate clinical management of RD. Herein, we provide a comprehensive overview on the progression of clinical trials for RD treatment using four types of stem/progenitor cell-based transplantation to replace degenerative retinal cells and/or to supplement trophic factors from the aspects of safety, effectiveness and their respective advantages and disadvantages. In addition, we also discuss the emerging role of stem cells in the secretion of multifunctional nanoscale exosomes by which stem cells could be further exploited as a potential RD therapy. This review will facilitate the understanding of scientists and clinicians of the enormous promise of stem/progenitor cell-based transplantation for RD treatment, and provide incentive for superior employment of such strategies that may be suitable for treatment of other diseases, such as stroke and ischaemia–reperfusion injury.

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Exosomes Derived From Mesenchymal Stem Cells Modulate miR-126 to Ameliorate Hyperglycemia-Induced Retinal Inflammation Via Targeting HMGB1

Abstract: Exosomes derived from mesenchymal stem cells modulate miR-126 to ameliorate hyperglycemia-induced retinal inflammation via targeting HMGB1.

Cited by 173 publications

References 35 publications

Immunoregulatory role of exosomes derived from differentiating mesenchymal stromal cells on inflammation and osteogenesis

Immunoregulatory role of exosomes derived from differentiating mesenchymal stromal cells on inflammation and osteogenesis

High Mobility Group Box-1 and Diabetes Mellitus Complications: State of the Art and Future Perspectives

Stem/progenitor cell-based transplantation for retinal degeneration: a review of clinical trials

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