Cardioprotection by cardiac progenitor cell-secreted exosomes: role of pregnancy-associated plasma protein-A

Barile, Lucio; Cervio, Elisabetta; Lionetti, Vincenzo; Milano, Giuseppina; Ciullo, Alessandra; Biemmi, Vanessa; Bolis, Sara; Altomare, Claudia; Matteucci, Marco; Silvestre, Dario Di; Brambilla, Francesca; Fertig, Tudor Emanuel; Torre, Tiziano; Demertzis, Stefanos; Mauri, Pierluigi; Moccetti, Tiziano; Vassalli, Giuseppe

doi:10.1093/cvr/cvy055

Cited by 173 publications

(192 citation statements)

References 32 publications

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“…Bian et al29 found the same results when they treated the rats with AMI with exosome extracted from human BMSCs. Through a comparison of cardiac‐resident progenitor cell–secreted exosomes and BMSC‐secreted exosomes, Barile et al30 explained that the cardioprotection of exosomes may act via the pregnancy‐associated plasma protein‐A mediated insulin‐like growth factor‐1 release and subsequently modulate intracellular protein kinase B and extracellular signal regulated kinase 1/2 phosphorylation. Feng et al31 demonstrated that exosomes released from ischemic preconditioned MSCs contained an increased amount of miR‐22, which could exert a silence effect on methyl CpG binding protein 2 to ameliorate apoptosis in mice with AMI.…”

Section: Discussionmentioning

confidence: 99%

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Wang

Chen

Zhao

et al. 2018

JAHA

283

206

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BackgroundExosomes are membranous vesicles generated by almost all cells. Recent studies demonstrated that mesenchymal stem cell–derived exosomes possessed many effects, including antiapoptosis, anti‐inflammatory effects, stimulation of angiogenesis, anticardiac remodeling, and recovery of cardiac function on cardiovascular diseases. However, targeting of exosomes to recipient cells precisely in vivo still remains a problem. Ligand fragments or homing peptides discovered by phage display and in vivo biopanning methods fused to the enriched molecules on the external part of exosomes have been exploited to improve the ability of exosomes to target specific tissues or organs carrying cognate receptors. Herein, we briefly elucidated how to improve targeting ability of exosomes to ischemic myocardium.Methods and ResultsWe used technology of molecular cloning and lentivirus packaging to engineer exosomal enriched membrane protein (Lamp2b) fused with ischemic myocardium‐targeting peptide CSTSMLKAC (IMTP). In vitro results showed that IMTP‐exosomes could be internalized by hypoxia‐injured H9C2 cells more efficiently than blank‐exosomes. Compared with blank‐exosomes, IMTP‐exosomes were observed to be increasingly accumulated in ischemic heart area (P<0.05). Meanwhile, attenuated inflammation and apoptosis, reduced fibrosis, enhanced vasculogenesis, and cardiac function were detected by mesenchymal stem cell–derived IMTP‐exosome treatment in ischemic heart area.ConclusionsOur research concludes that exosomes engineered by IMTP can specially target ischemic myocardium, and mesenchymal stem cell–derived IMTP‐exosomes exert enhanced therapeutic effects on acute myocardial infarction.

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Section: Discussionmentioning

confidence: 99%

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Wang

Chen

Zhao

et al. 2018

JAHA

283

206

View full text Add to dashboard Cite

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“…Interestingly, NT5E (CD73) and ENG (CD105), two of the minimally required cell surface antigens for MSC were detected in seven out of ten, and THY1 (CD90), in eight out of ten datasets (Table ). Please note that some datasets contain relatively low amounts of reported IDs (<500), which can be explained by that fact that one datasets only reports quantified IDs, and that for two other studies, the proteomics approach was limited to identifying only the relatively more abundant proteins …”

Section: Resultsmentioning

confidence: 99%

Proteomic Signature of Mesenchymal Stromal Cell‐Derived Small Extracellular Vesicles

et al. 2019

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Small extracellular vesicles (EVs) are 50–200 nm vesicles secreted by most cells. They are considered as mediators of intercellular communication, and EVs from specific cell types, in particular mesenchymal stem/stromal cells (MSCs), offer powerful therapeutic potential, and can provide a novel therapeutic strategy. They appear promising and safe (as EVs are non‐self‐replicating), and eventually MSC‐derived EVs (MSC‐EVs) may be developed to standardized, off‐the‐shelf allogeneic regenerative and immunomodulatory therapeutics. Promising pre‐clinical data have been achieved using MSCs from different sources as EV‐producing cells. Similarly, a variety EV isolation and characterization methods have been applied. Interestingly, MSC‐EVs obtained from different sources and prepared with different methods show in vitro and in vivo therapeutic effects, indicating that isolated EVs share a common potential. Here, well‐characterized and controlled, publicly available proteome profiles of MSC‐EVs are compared to identify a common MSC‐EV protein signature that might be coupled to the MSC‐EVs’ common therapeutic potential. This protein signature may be helpful in developing MSC‐EV quality control platforms required to confirm the identity and test for the purity of potential therapeutic MSC‐EVs.

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“…Independent landmark studies reported that exosomes released by human CPCs or human cardiosphere‐derived cells (CDCs) inhibit apoptosis and promote the proliferation of cardiomyocytes, while enhancing angiogenesis. Exosomes from both CDCs and CPCs reduce scar size and improve ventricular function in rodent MI models, the latter being more cardioprotective than bone marrow‐MSC exosomes derived from the same patients, when compared with dermal fibroblast exosomes . Cardioprotective effects are also induced ‘in vitro’ and ‘in vivo’ by cardiac fibroblast exosomes, while those released from human normal dermal fibroblasts do not exert these beneficial effects .…”

Section: Cell‐free Cardiac Regenerationmentioning

confidence: 99%

“…Exosomes from both CDCs and CPCs reduce scar size and improve ventricular function in rodent MI models, 38,39 the latter being more cardioprotective than bone marrow-MSC exosomes derived from the same patients, when compared with dermal fibroblast exosomes. 40 Cardioprotective effects are also induced 'in vitro' and 'in vivo' by cardiac fibroblast exosomes, 41 while those released from human normal dermal fibroblasts do not exert these beneficial effects. 38,40 Finally, BMC and CPCs exosomes increase blood vessel density in the infarct region.…”

Section: Cell-free C Ard Iac Reg Ener Ati Onmentioning

confidence: 99%

Turning regenerative technologies into treatment to repair myocardial injuries

Carotenuto

Teodori

Maccari

et al. 2019

J Cellular Molecular Medi

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Regenerative therapies including stem cell treatments hold promise to allow curing patients affected by severe cardiac muscle diseases. However, the clinical efficacy of stem cell therapy remains elusive, so far. The two key roadblocks that still need to be overcome are the poor cell engraftment into the injured myocardium and the limited knowledge of the ideal mixture of bioactive factors to be locally delivered for restoring heart function. Thus, therapeutic strategies for cardiac repair are directed to increase the retention and functional integration of transplanted cells in the damaged myocardium or to enhance the endogenous repair mechanisms through cell‐free therapies. In this context, biomaterial‐based technologies and tissue engineering approaches have the potential to dramatically impact cardiac translational medicine. This review intends to offer some consideration on the cell‐based and cell‐free cardiac therapies, their limitations and the possible future developments.

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Cardioprotection by cardiac progenitor cell-secreted exosomes: role of pregnancy-associated plasma protein-A

Cited by 173 publications

References 32 publications

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Engineered Exosomes With Ischemic Myocardium‐Targeting Peptide for Targeted Therapy in Myocardial Infarction

Proteomic Signature of Mesenchymal Stromal Cell‐Derived Small Extracellular Vesicles

Turning regenerative technologies into treatment to repair myocardial injuries

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