Extracellular vesicles secreted from mesenchymal stem cells exert anti-apoptotic and anti-inflammatory effects via transmitting microRNA-18b in rats with diabetic retinopathy

Xu, Ze-Peng; Tian, Ni; Li, Songtao; Li, Kunmeng; Guo, Haike; Zhang, Hongyang; Jin, Haiying; An, Meixia; Yu, Xiaoyi

doi:10.1016/j.intimp.2021.108234

Cited by 28 publications

(16 citation statements)

References 35 publications

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“…While approaches to improve MSC-based anti-apoptotic effects on cardiomyocytes have shown promising results both in vitro and in vivo [ 30 , 32 , 33 , 59 ], very few studies have investigated the anti-apoptotic paracrine effects mediated by MSC on endothelial cells. Only data on tunneling nanotubes [ 60 ] and extracellular vesicles derived from MSC have been reported to repress high glucose (HG) [ 61 ] or serum deprivation-induced apoptosis [ 62 , 63 ]. Our present results obtained on a human endothelial cell line reveal, for the first time, that MSC pharmacologically preconditioned are able to provide an enhanced paracrine anti-apoptotic effect.…”

Section: Discussionmentioning

confidence: 99%

PPARβ/δ priming enhances the anti-apoptotic and therapeutic properties of mesenchymal stromal cells in myocardial ischemia–reperfusion injury

et al. 2022

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Background Mesenchymal Stromal Cells (MSC) have been widely used for their therapeutic properties in many clinical applications including myocardial infarction. Despite promising preclinical results and evidences of safety and efficacy in phases I/ II, inconsistencies in phase III trials have been reported. In a previous study, we have shown using MSC derived from the bone marrow of PPARβ/δ (Peroxisome proliferator-activated receptors β/δ) knockout mice that the acute cardioprotective properties of MSC during the first hour of reperfusion are PPARβ/δ-dependent but not related to the anti-inflammatory effect of MSC. However, the role of the modulation of PPARβ/δ expression on MSC cardioprotective and anti-apoptotic properties has never been investigated. Objectives The aim of this study was to investigate the role of PPARβ/δ modulation (inhibition or activation) in MSC therapeutic properties in vitro and ex vivo in an experimental model of myocardial infarction. Methods and results Naïve MSC and MSC pharmacologically activated or inhibited for PPARβ/δ were challenged with H2O2. Through specific DNA fragmentation quantification and qRT-PCR experiments, we evidenced in vitro an increased resistance to oxidative stress in MSC pre-treated by the PPARβ/δ agonist GW0742 versus naïve MSC. In addition, PPARβ/δ-priming allowed to reveal the anti-apoptotic effect of MSC on cardiomyocytes and endothelial cells in vitro. When injected during reperfusion, in an ex vivo heart model of myocardial infarction, 3.75 × 105 PPARβ/δ-primed MSC/heart provided the same cardioprotective efficiency than 7.5 × 105 naïve MSC, identified as the optimal dose in our experimental model. This enhanced short-term cardioprotective effect was associated with an increase in both anti-apoptotic effects and the number of MSC detected in the left ventricular wall at 1 h of reperfusion. By contrast, PPARβ/δ inhibition in MSC before their administration in post-ischemic hearts during reperfusion decreased their cardioprotective effects. Conclusion Altogether these results revealed that PPARβ/δ-primed MSC exhibit an increased resistance to oxidative stress and enhanced anti-apoptotic properties on cardiac cells in vitro. PPARβ/δ-priming appears as an innovative strategy to enhance the cardioprotective effects of MSC and to decrease the therapeutic injected doses. These results could be of major interest to improve MSC efficacy for the cardioprotection of injured myocardium in AMI patients.

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Section: Discussionmentioning

confidence: 99%

PPARβ/δ priming enhances the anti-apoptotic and therapeutic properties of mesenchymal stromal cells in myocardial ischemia–reperfusion injury

et al. 2022

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“…In the treatment of DR, miR-192 in MSC-EVs could target and negatively regulate ITGA1, thereby ameliorating diabetic retinal damage by decreasing the inflammatory response and angiogenesis [ 149 ]. Similarly, hucMSC-derived small EVs could upregulate miR-18b and reduce retinal vascular leakage and retinal thickness [ 150 ]. Overall, these findings provide new insights into EV-based therapy for DR.…”

Section: Evs In Aging-related Diseasesmentioning

confidence: 99%

Diagnostic and Therapeutic Roles of Extracellular Vesicles in Aging-Related Diseases

Sun

Hou

Zhang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Aging shows a decline in overall physical function, and cellular senescence is the powerful catalyst leading to aging. Considering that aging will be accompanied with the emergence of various aging-related diseases, research on new antiaging drugs is still valuable. Extracellular vesicles (EVs), as tools for intercellular communication, are important components of the senescence-associated secretory phenotype (SASP), and they can play pathological roles in the process of cellular senescence. In addition, EVs are similar to their original cells in functions. Therefore, EVs derived from pathological tissues or body fluids may be closely related to the progression of diseases and become potential biomarkers, while those from healthy cells may have therapeutic effects. Moreover, EVs are satisfactory drug carriers. At present, numerous studies have supported the idea that engineered EVs could improve drug targeting ability and utilization efficiency. Here, we summarize the characteristics of EVs and cellular senescence and focus on the diagnostic and therapeutic potential of EVs in various aging-related diseases, including Alzheimer disease, osteoporosis, cardiovascular disease, diabetes mellitus and its complications, and skin aging.

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“…EVs do not just contain miRNAs; they also deliver miRNAs to cells. EVs secreted from mesenchymal stem cells inhibit apoptosis and reduce inflammatory responses by targeting miRNA-18b in ECs [ 60 ]. Although the biology of EVs in DR is not well investigated, its important role in DR has been recognized [ 61 ].…”

Section: Mirnasmentioning

confidence: 99%

Noncoding RNAs Are Promising Therapeutic Targets for Diabetic Retinopathy: An Updated Review (2017–2022)

Wang

Jin

et al. 2022

Biomolecules

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Diabetic retinopathy (DR) is the most common complication of diabetes. It is also the main cause of blindness caused by multicellular damage involving retinal endothelial cells, ganglial cells, and pigment epithelial cells in adults worldwide. Currently available drugs for DR do not meet the clinical needs; thus, new therapeutic targets are warranted. Noncoding RNAs (ncRNAs), a new type of biomarkers, have attracted increased attention in recent years owing to their crucial role in the occurrence and development of DR. NcRNAs mainly include microRNAs, long noncoding RNAs, and circular RNAs, all of which regulate gene and protein expression, as well as multiple biological processes in DR. NcRNAs, can regulate the damage caused by various retinal cells; abnormal changes in the aqueous humor, exosomes, blood, tears, and the formation of new blood vessels. This study reviews the different sources of the three ncRNAs—microRNAs, long noncoding RNAs, and circular RNAs—involved in the pathogenesis of DR and the related drug development progress. Overall, this review improves our understanding of the role of ncRNAs in various retinal cells and offers therapeutic directions and targets for DR treatment.

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Extracellular vesicles secreted from mesenchymal stem cells exert anti-apoptotic and anti-inflammatory effects via transmitting microRNA-18b in rats with diabetic retinopathy

Cited by 28 publications

References 35 publications

PPARβ/δ priming enhances the anti-apoptotic and therapeutic properties of mesenchymal stromal cells in myocardial ischemia–reperfusion injury

PPARβ/δ priming enhances the anti-apoptotic and therapeutic properties of mesenchymal stromal cells in myocardial ischemia–reperfusion injury

Diagnostic and Therapeutic Roles of Extracellular Vesicles in Aging-Related Diseases

Noncoding RNAs Are Promising Therapeutic Targets for Diabetic Retinopathy: An Updated Review (2017–2022)

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