Targeted delivery of extracellular vesicles in heart injury

Chen, Peier; Wang, Ling; Fan, Xianglin; Ning, Xiaodong; Yu, Bin; Ou, Caiwen; Chen, Minsheng

doi:10.7150/thno.51571

Cited by 62 publications

(54 citation statements)

References 82 publications

(91 reference statements)

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“…EVs can also convey RNAs, including mRNAs, miRNAs, and lncRNAs, which represent their cells of origin [ 78 , 79 , 80 , 81 , 82 , 83 , 84 ]. Interestingly, EVs possess the capacity to transfer specific proteins and genetic materials to the recipient cells and, also, EV membranes can be engineered using organ-specific therapeutic proteins or drugs for treating the incurable disease of target organs [ 85 , 86 , 87 , 88 , 89 , 90 ]. Moreover, the application of EVs obviates the biosafety issues incurred by the direct application of whole stem cells, including tumorigenicity and immunogenic reactions [ 91 , 92 ].…”

Section: Discussionmentioning

confidence: 99%

High Therapeutic and Esthetic Properties of Extracellular Vesicles Produced from the Stem Cells and Their Spheroids Cultured from Ocular Surgery-Derived Waste Orbicularis Oculi Muscle Tissues

et al. 2021

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Extracellular vesicles (EVs) are paracrine factors that mediate stem cell therapeutics. We aimed at evaluating the possible therapeutic and esthetic applications of EVs prepared from the waste human facial tissue-derived orbicularis oculi muscle stem cells (OOM-SCs). OOM-SCs were isolated from the ocular tissues (from elders and youngsters) after upper eyelid blepharoplasty or epiblepharon surgeries. EVs were prepared from the OOM-SCs (OOM-SC-EVs) and their three-dimensional spheroids. OOM-SCs showed a spindle-like morphology with trilineage differentiation capacity, positive expression of CD105, CD 90, and CD73, and negative expression of CD45 and CD34, and their stem cell properties were compared with other adult mesenchymal stem cells. OOM-SC-EVs showed a high inhibitory effect on melanin synthesis in B16F10 cells by blocking tyrosinase activity. OOM-SC-EVs treatment led to a significant attenuation of senescence-associated changes, a decrease in reactive oxygen species generation, and an upregulation of antioxidant genes. We demonstrated the regeneration activity of OOM-SC-EVs in in vitro wound healing of normal human dermal fibroblasts and upregulation of anti-wrinkle-related genes and confirmed the therapeutic potential of OOM-SC-EVs in the healing of the in vivo wound model. Our study provides promising therapeutic and esthetic applications of OOM-SC-EVs, which can be obtained from the ocular surgery-derived waste human facial tissues.

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Section: Discussionmentioning

confidence: 99%

High Therapeutic and Esthetic Properties of Extracellular Vesicles Produced from the Stem Cells and Their Spheroids Cultured from Ocular Surgery-Derived Waste Orbicularis Oculi Muscle Tissues

et al. 2021

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“…Studies have shown that EVs in circulation tend to have a short half‐life on the order of just over an hour, after which time they are preferentially sequestered in organs such as the liver, lung, and spleen where they can be quickly phagocytized and cleared by macrophages. [ 145 ] These mechanisms of clearance mean that few EVs may actually reach and interact with target cells in the myocardium, possibly rendering EV therapeutics ineffective at clinically viable doses even if efficacy can be shown at the preclinical stage. EVs can also be infused into circulation directly within the coronary arteries to attempt to enhance local delivery and uptake in the heart, termed “intracoronary delivery.” Gallet et al tested intracoronary infusion of cardiosphere‐derived cell (CDC) EVs in a porcine model of acute MI.…”

Section: Harnessing the Power Of Evs In Cardiac Diagnostics And Regenerative Therapeuticsmentioning

confidence: 99%

“…Intramyocardial injections have proven to be a more effective method for cardiac‐specific delivery, but injected EVs can still escape the heart through leakage from the needle hole as well as venous drainage. [ 145,147 ] Thus, representative studies have found that significant myocardial retention and uptake of EVs is still limited to window of a few hours postinjection. [ 12 ]…”

Section: Harnessing the Power Of Evs In Cardiac Diagnostics And Regenerative Therapeuticsmentioning

confidence: 99%

“…Hydrogels and other scaffolds with encapsulated EVs can also be prepared ex vivo and surgically implanted onto the heart for sustained release directly to the site of cardiac injury. [ 145 ] In both cases, improved retention and sustained release of EVs for up to 3 weeks has been observed in vivo. [ 12,145 ] In one such in vivo study, Liu et al encapsulated iPS or CM EVs in collagen gelfoam mesh patches that were applied to rat hearts immediately after left anterior descending artery ligation, as shown in Figure 5c.…”

Section: Harnessing the Power Of Evs In Cardiac Diagnostics And Regenerative Therapeuticsmentioning

confidence: 99%

“…[ 145 ] In both cases, improved retention and sustained release of EVs for up to 3 weeks has been observed in vivo. [ 12,145 ] In one such in vivo study, Liu et al encapsulated iPS or CM EVs in collagen gelfoam mesh patches that were applied to rat hearts immediately after left anterior descending artery ligation, as shown in Figure 5c. Their results show in Figure 5d demonstrated that CM EV patches significantly increased ejection fraction of injured hearts after 24 h compared with control and iPS EV groups.…”

Section: Harnessing the Power Of Evs In Cardiac Diagnostics And Regenerative Therapeuticsmentioning

confidence: 99%

See 2 more Smart Citations

A New Role for Extracellular Vesicles in Cardiac Tissue Engineering and Regenerative Medicine

Wagner

Radišić

2021

Advanced NanoBiomed Research

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Cardiovascular diseases are the leading cause of death worldwide. Discovering new therapies to treat heart disease requires improved understanding of cardiac physiology at a cellular level. Extracellular vesicles (EVs) are plasma membrane‐bound nano‐ and microparticles secreted by cells and known to play key roles in intercellular communication, often through transfer of biomolecular cargo. Advances in EV research have established techniques for EV isolation from tissue culture media or biofluids, as well as standards for quantitation and biomolecular characterization. EVs released by cardiac cells are known to be involved in regulating cardiac physiology as well as in the progression of myocardial diseases. Due to difficulty accessing the heart in vivo, advanced in vitro cardiac “tissues‐on‐a‐chip” have become a recent focus for studying EVs in the heart. These physiologically relevant models are producing new insight into the role of EVs in cardiac physiology and disease while providing a useful platform for screening novel EV‐based therapeutics for cardiac tissue regeneration post‐injury. Numerous hurdles have stalled the clinical translation of EV therapeutics for heart patients, but tissue‐on‐a‐chip models are playing an important role in bridging the translational gap, improving mechanistic understanding of EV signaling in cardiac physiology, disease, and repair.

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Bioengineering Extracellular Vesicles for the Treatment of Cardiovascular Diseases

Ramasubramanian

Gidda

et al. 2022

Advanced Biology

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contributing factors of these diseases are numerous, including genetics, diet, smoking, and lack of exercise. [1][2][3] With development of angiography, drug-eluting stents, balloon catheters, bypass surgery, and new disease-modifying drug therapies, there has been significant improvement in the care and treatment of patients with CVD. [4] Despite these innovations and progress, CVD is still the leading cause of death in the US and worldwide. Furthermore, these treatment options bring their own set of complications, including intimal hyperplasia and thrombosis, as well as drug therapy side effects. Therefore, broader therapeutic interventions are still needed in order to ameliorate the devastating impacts of CVD. Recently, a new class of therapeutics has emerged that is known as extracellular vesicles (EVs). EVs are membranebound vesicles released by different types of prokaryotic and eukaryotic cells, and are ubiquitously found in most body fluids such as blood, urine, breast milk, saliva, and cerebrospinal fluid. [5] In general, EVs can be classified into three subclasses which are differentiated by their biogenesis mechanisms. [5,6] The first class of EVs is microvesicles, also known as ectosomes or microparticles. They are produced by the outward budding and fission of the plasma membrane and range from 50 nm to 1 micron in size. [7,8] The second EV subset are termed apoptotic bodies (50 nm to 5 microns) and are released when plasma membrane blebbing occurs during late apoptosis. The final EV subset is known as exosomes. Exosomes are the smallest type of EV (also often referred to as sEV), ranging between 50-150 nm, and originate from the inward budding of multivesicular bodies (MVB). Exosomes are released into the extracellular space upon fusion of MVBs with the plasma membrane, specifically at the lipid raft subdomains. [9,10] All subsets of vesicles contain bioactive cargo, including proteins, mRNAs, microRNAs (miRNAs, miRs), and lipids, that are efficiently delivered to recipient cells to regulate different biological processes. [6,8,[11][12][13] Within the cardiovascular system, EVs play important roles in maintaining normal physiological function by facilitating cellular crosstalk. [8,11,14] Under disease or injury conditions, EV phenotypes are seen to shift in order to indicate cardiovascular dysfunction and to restore physiological balance. However, administration of EVs as therapeutics has been limited due to difficulties in isolation and standardization, ineffective targeting, and poor retention. [15,16] Advances in research and technology have addressed these challenges by engineering EVs to augment Cardiovascular diseases (CVD) remain one of the leading causes of mortality worldwide. Despite recent advances in diagnosis and interventions, there is still a crucial need for new multifaceted therapeutics that can address the complicated pathophysiological mechanisms driving CVD. Extracellular vesicles (EVs) are nanovesicles that are secreted by all types of cells to transport molecular cargo and regu...

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Targeted delivery of extracellular vesicles in heart injury

Cited by 62 publications

References 82 publications

High Therapeutic and Esthetic Properties of Extracellular Vesicles Produced from the Stem Cells and Their Spheroids Cultured from Ocular Surgery-Derived Waste Orbicularis Oculi Muscle Tissues

High Therapeutic and Esthetic Properties of Extracellular Vesicles Produced from the Stem Cells and Their Spheroids Cultured from Ocular Surgery-Derived Waste Orbicularis Oculi Muscle Tissues

A New Role for Extracellular Vesicles in Cardiac Tissue Engineering and Regenerative Medicine

Bioengineering Extracellular Vesicles for the Treatment of Cardiovascular Diseases

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