Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model

Bian, Su-Yan; Zhang, Liping; Liufa, Duan; Wang, Xi; Min, Ying; Yu, Hanjie

doi:10.1007/s00109-013-1110-5

Cited by 613 publications

(483 citation statements)

References 50 publications

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“…They further elaborated that MSCs‐exosomes had an antiapoptotic effect on AMI through activation of protein kinase B and glycogen synthase kinase 3 and inhibition of c‐Jun N‐terminal kinase. 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.…”

Section: Discussionmentioning

confidence: 67%

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

Wang

Chen

Zhao

et al. 2018

JAHA

290

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: 67%

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

Wang

Chen

Zhao

et al. 2018

JAHA

290

206

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“…In recent years, the therapeutic properties of MSCs have been considered to be due to the therapeutic effect of the secretome, especially EVs 80. A number of preclinical studies, including of ischemia, neurodegenerative diseases, fibrotic liver, and acute kidney injury, have explored the potential efficacy of MSC‐derived EVs in tissue regeneration 81, 82, 83. In addition, the immune‐suppressive capacity of MSC‐derived EVs, as a result of the proteins and RNAs they transport, has been recognized to regulate immunity via the release of anti‐inflammatory cytokines or modulation of the Toll‐like receptor signaling pathway 84…”

Section: Achievements and Limitations Of Cell‐free Therapy Using Natimentioning

confidence: 99%

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

2018

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Extracellular vesicles (EVs) are ubiquitous nanosized membrane vesicles consisting of a lipid bilayer enclosing proteins and nucleic acids, which are active in intercellular communications. EVs are increasingly seen as a vital component of many biological functions that were once considered to require the direct participation of stem cells. Consequently, transplantation of EVs is gradually becoming considered an alternative to stem cell transplantation due to their significant advantages, including their relatively low probability of neoplastic transformation and abnormal differentiation. However, as research has progressed, it is realized that EVs derived from native‐source cells may have various shortcomings, which can be corrected by modification and optimization. To date, attempts are made to modify or improve almost all the components of EVs, including the lipid bilayer, proteins, and nucleic acids, launching a new era of modularized EV therapy through the “modular design” of EV components. One high‐yield technique, generating EV mimetic nanovesicles, will help to make industrial production of modularized EVs a reality. These modularized EVs have highly customized “modular design” components related to biological function and targeted delivery and are proposed as a promising approach to achieve personalized and precision medicine.

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“…For example, therapeutic activities in adipose-derived mesenchymal stem cells (AT-MSCs) are mediated by EVs along with other paracrine signalling routes [8,9]. The MSC EVs have a unique capability to induce regeneration of damaged tissues offering a paradigm shift towards cell-free therapy [10,11]. …”

Section: Introductionmentioning

confidence: 99%

Efficient ultrafiltration‐based protocol to deplete extracellular vesicles from fetal bovine serum

Kornilov

Puhka

Mannerström

et al. 2018

J of Extracellular Vesicle

156

125

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Fetal bovine serum (FBS) is the most commonly used supplement in studies involving cell-culture experiments. However, FBS contains large numbers of bovine extracellular vesicles (EVs), which hamper the analyses of secreted EVs from the cell type of preference and, thus, also the downstream analyses. Therefore, a prior elimination of EVs from FBS is crucial. However, the current methods of EV depletion by ultracentrifugation are cumbersome and the commercial alternatives expensive. In this study, our aim was to develop a protocol to completely deplete EVs from FBS, which may have wide applicability in cell-culture applications. We investigated different EV-depleted FBS prepared by our novel ultrafiltration-based protocol, by conventionally used overnight ultracentrifugation, or commercially available depleted FBS, and compared them with regular FBS. All sera were characterized by nanoparticle tracking analysis, electron microscopy, Western blotting and RNA quantification. Next, adipose-tissue mesenchymal stem cells (AT-MSCs) and cancer cells were grown in the media supplemented with the three different EV-depleted FBS and compared with cells grown in regular FBS media to assess the effects on cell proliferation, stress, differentiation and EV production. The novel ultrafiltration-based protocol depleted EVs from FBS clearly more efficiently than ultracentrifugation and commercial methods. Cell proliferation, stress, differentiation and EV production of AT-MSCs and cancer cell lines were similarly maintained in all three EV-depleted FBS media up to 96 h. In summary, our ultrafiltration protocol efficiently depletes EVs, is easy to use and maintains cell growth and metabolism. Since the method is also cost-effective and easy to standardize, it could be used in a wide range of cell-culture applications helping to increase comparability of EV research results between laboratories.

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Extracellular vesicles derived from human bone marrow mesenchymal stem cells promote angiogenesis in a rat myocardial infarction model

Cited by 613 publications

References 50 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

Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

Efficient ultrafiltration‐based protocol to deplete extracellular vesicles from fetal bovine serum

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