Extracellular vesicles derived from mesenchymal stem cells induce features of diabetic retinopathy in vitro

Beltramo, Elena; Lopatina, Tatiana; Berrone, Elena; Mazzeo, Aurora; Iavello, Alessandra; Camussi, Giovanni; Porta, Massimo

doi:10.1007/s00592-014-0672-1

Cited by 44 publications

(44 citation statements)

References 37 publications

(56 reference statements)

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“…In agreement with a recent study showing that extracellular vesicles derived from the mesenchymal stem cells increased the blood–retina permeability in an in vitro model of diabetic retinopathy (Beltramo et al. ), one may discuss whether the BMSCs in our study had a similar, however, not statistically significant, effect. Although previous studies revealed that BMSCs could transdifferentiate into retinal pigment epithelium cells, photoreceptors in vitro and/or in vivo , and in vascular endothelial cells (Zhen‐Zhou et al.…”

Section: Discussionsupporting

confidence: 93%

“…4B). In agreement with a recent study showing that extracellular vesicles derived from the mesenchymal stem cells increased the blood-retina permeability in an in vitro model of diabetic retinopathy (Beltramo et al 2014), one may discuss whether the BMSCs in our study had a similar, however, not statistically significant, effect. Although previous studies revealed that BMSCs could transdifferentiate into retinal pigment epithelium cells, photoreceptors in vitro and/or in vivo, and in vascular endothelial cells (Zhen-Zhou et al 2008), our study suggested that BMSCs were helpful for the regeneration and remodelling of injured vessels in retinopathy of prematurity models, without transdifferentiating into endothelial cells but by supporting a normal endothelial regeneration.…”

Section: Discussionsupporting

confidence: 93%

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Human bone marrow mesenchymal stem cells for retinal vascular injury

Wang

Zhang

et al. 2016

Acta Ophthalmologica

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 93%

Human bone marrow mesenchymal stem cells for retinal vascular injury

Wang

Zhang

et al. 2016

Acta Ophthalmologica

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“…The primary involvement of hyperglycaemia in these events is well known (Beltramo & Porta ), with either direct or mediated actions (Beltramo et al. ; Mazzeo et al. ), but similar effects of hypoxia have been also recently described (Aplin & Nicosia ).…”

Section: Discussionmentioning

confidence: 94%

Imbalance between pro‐apoptotic and pro‐survival factors in human retinal pericytes in diabetic‐like conditions

Beltramo

Arroba

Mazzeo

et al. 2017

Acta Ophthalmologica

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Purpose Loss of pericytes is one the key events in the pathogenesis of diabetic retinopathy. We have previously demonstrated that human retinal pericytes (HRP) are more vulnerable to intermittent than stable high glucose concentrations, with an increase in apoptosis. Our aim was to explore the expression of molecules involved in pro‐apoptotic and survival pathways in pericytes cultured in stable/intermittent high glucose and/or hypoxia, to clarify the mechanisms of action of these diabetic‐like stressing stimuli. Methods Human retinal pericytes (HRP) were exposed intermittently at 48‐hr intervals to high/physiological glucose for 8 days (intHG) and/or hypoxia over the last 48 hr. Control cells were kept in stable physiological and high glucose. Cell proliferation and apoptosis were assessed. The expression of pro‐apoptotic and pro‐survival molecules was evaluated by Western blotting. Caspase‐8 translocation from the cytoplasm into the nucleus was checked by Western blotting of nuclear versus cytoplasmic fractions and immunofluorescence. Results Hypoxia, alone and combined with intHG, increased HRP apoptosis and decreased proliferation. Pro‐apoptotic molecules increased in HRP cultured in these conditions, while some survival markers decreased. Conversely, in stable HG, pro‐apoptotic molecules were stable or even decreased, and survival factors increased. Translocation of caspase‐8 from cytoplasm into nucleus indicates a primary role for this molecule in inducing apoptosis. Conclusion Diabetic‐like conditions are able to stimulate pericyte apoptosis through activation of pro‐apoptotic molecules, leading to an imbalance between pro‐apoptotic and survival signalling pathways, with caspase‐8 playing a pivotal role. Our identification of such intermediates could help finding new therapeutic approaches for the prevention of diabetic retinopathy.

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“…Moreover, EV added to EC/pericytes co‐cultures in matrigel promoted in vitro angiogenesis in a matrix metalloproteinase‐2‐dependent manner. Via these properties of microvessel remodeling, EV are an important element in the early stages of diabetic retinopathy pathogenesis …”

Section: Effects Of Ev On Endothelial Cellsmentioning

confidence: 99%

Extracellular vesicles and microvascular pathology: Decoding the active dialogue

Hosseini‐Beheshti

Grau

2018

Microcirculation

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Extracellular vesicles (EV) are a heterogeneous collection of membrane‐surrounded structures released from all studied cells, under both physiological and pathological conditions. These nano‐size vesicles carry complex cargoes including different classes of proteins, lipids and nucleic acids and are known to act as a communication and signalling vesicles in various cellular process. In addition to their role in development and progression of pathological disorders which make them potentially great biomarkers, EV have beneficial effects, as they take part in homeostasis. In this review we have analysed the evidence for the role of microvesicles and exosomes secreted from other cells on microvascular endothelium (EV uptake) as well as the role of endothelial‐derived vesicles on their neighbouring and distant cells (EV release).

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Extracellular vesicles derived from mesenchymal stem cells induce features of diabetic retinopathy in vitro

Cited by 44 publications

References 37 publications

Human bone marrow mesenchymal stem cells for retinal vascular injury

Human bone marrow mesenchymal stem cells for retinal vascular injury

Imbalance between pro‐apoptotic and pro‐survival factors in human retinal pericytes in diabetic‐like conditions

Extracellular vesicles and microvascular pathology: Decoding the active dialogue

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