Exosomes and Exosomal Non-coding RNAs Are Novel Promises for the Mechanism-Based Diagnosis and Treatments of Atrial Fibrillation

Abstract

Atrial fibrillation (AF) is the most common arrhythmia worldwide and has a significant impact on human health and substantial costs. Currently, there is a lack of accurate biomarkers for the diagnosis and prognosis of AF. Moreover, the long-term efficacy of the catheter ablation in the AF is unsatisfactory. Therefore, it is necessary to explore new biomarkers and treatment strategies for the mechanism-based AF. Exosomes are nano-sized biovesicles released by nearly all types of cells. Since the AF would be linked to the changes of the atrial cells and their microenvironment, and the AF would strictly influence the exosomal non-coding RNAs (exo-ncRNAs) expression, which makes them as attractive diagnostic and prognostic biomarkers for the AF. Simultaneously, the exo-ncRNAs have been found to play an important role in the mechanisms of the AF and have potential therapeutic prospects. Although the role of the exo-ncRNAs in the AF is being actively investigated, the evidence is still limited. Furthermore, there is a lack of consensus regarding the most appropriate approach for exosome isolation and characterization. In this article, we reviewed the new methodologies available for exosomes biogenesis, isolation, and characterization, and then discussed the mechanism of the AF and various levels and types of exosomes relevant to the AF, with the special emphasis on the exo-ncRNAs in the diagnosis, prognosis, and treatment of the mechanism-based AF.

Delivery of Stem Cell Secretome for Therapeutic Applications

“…Stem cell secretome contained protein compositions and extracellular vesicles with a series of masses and sizes, which could be classified by ultrafiltration and specific density gradient centrifugation. 37,38 proteins with masses >50, 50−30, 30−10, and 10−3 kDa. 51 Interestingly, only fractions from 10 to 30 kDa significantly reduced the level of liver enzymes in acetaminophen-induced acute liver failure.…”

“…To further separate the specific vesicles, additional purification steps, such as ultrafiltration and density gradient, are required. , Different and specific isolation methods have effects on the quality of secretome. Stem cell secretome contained protein compositions and extracellular vesicles with a series of masses and sizes, which could be classified by ultrafiltration and specific density gradient centrifugation. , Temnov et al normalized mesenchymal stem cells conditioned medium fractions by volume, which predominantly contained proteins with masses >50, 50–30, 30–10, and 10–3 kDa . Interestingly, only fractions from 10 to 30 kDa significantly reduced the level of liver enzymes in acetaminophen-induced acute liver failure .…”

“…In addition, systemic flow after intravenous injection often results in significant loss in the infused cell-free products, thus calling for booster dosage. To tackle this issue, different platforms have been recently developed for sustained and controlled delivery of stem cell secretome. , Biomaterial-based platforms are popular and potential for the delivery of a more localized and concentrated dosage in the proximity of the target site, which include nanoparticles, injectable hydrogels, microneedles, and scaffold patches. − The biology and function of secretome have been well discussed in detail elsewhere. − Stem cell secretome for therapeutic applications can also be found in some comprehensive reviews, in which multiple diseases and their therapeutic mechanisms are well discussed. ,− However, few review articles focus on the optimization for high-output production of stem cell secretome or discuss the state-of-the-art delivery systems. The diverse emerging biomaterial-based platforms for the effective and efficient delivery of stem cell secretome deserve more attention.…”

Extracellular Vesicles in Atrial Fibrillation—State of the Art

“…Because EVs have been suggested to play a potential role in AF [ 13 , 14 , 15 , 16 , 17 ], the purpose of this review is to summarize the current data on EVs’ diagnostic and prognostic utility in AF patients.…”

“…EVs have also been extensively investigated in various cardiovascular diseases, in terms of their involvement in pathophysiology or being potential biomarkers, as their concentrations can be determined with the use of the accessible techniques, e.g., flow cytometry (Figure 1) [10][11][12]. Because EVs have been suggested to play a potential role in AF [13][14][15][16][17], the purpose of this review is to summarize the current data on EVs' diagnostic and prognostic utility in AF patients.…”