Treatment of infarcted heart tissue via the capture and local delivery of circulating exosomes through antibody-conjugated magnetic nanoparticles

Liu, Shiyu; Chen, Xin; Bao, Lili; Liu, Tao; Yuan, Pingyun; Yang, Xianghua; Qiu, Xinyu; Gooding, J. Justin; Bai, Yongkang; Xiao, Jiajia; Pu, Feng-Xing

doi:10.1038/s41551-020-00637-1

Cited by 202 publications

(157 citation statements)

References 51 publications

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“…We also separately detected the drug toxicity in the liver and lung and found that Exo-siRNAs had no significant toxic and side effects on the liver and lung. Besides, it is also reported that exosomes have satisfactory immunogenicity to target organs without harmful effects; and according to evidences from cell experiments, a cell-killing effect of exosomes has not been found [26]. Thus, we speculate that exosomes have nonsignificant toxicity to the liver, lung and other organs.…”

Section: Discussionmentioning

confidence: 76%

SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats

Huang

et al. 2021

Stem Cell Res Ther

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Background How to obtain a small interfering RNA (siRNA) vector has become a moot point in recent years. Exosomes (Exo) show advantages of long survival time in vivo, high transmission efficiency, and easy penetration across the blood-spinal cord barrier, renowned as excellent carriers of bioactive substances. Methods We applied mesenchymal stem cell (MSC)-derived exosomes as the delivery of synthesized siRNA, which were extracted from rat bone marrow. We constructed exosomes-siRNA (Exo-siRNA) that could specifically silence CTGF gene in the injury sites by electroporation. During the administration, we injected Exo-siRNA into the tail vein of SCI rats, Results In vivo and in vitro experiments showed that Exo-siRNA not only effectively inhibited the expressions of CTGF gene, but quenched inflammation, and thwarted neuronal apoptosis and reactive astrocytes and glial scar formation. Besides, it significantly upregulated several neurotrophic factors and anti-inflammatory factors, acting as a facilitator of locomotor recovery of rats with spinal cord injury (SCI). Conclusions In conclusion, this study has combined the thoroughness of gene therapy and the excellent drug-loading characteristics of Exo for the precise treatment of SCI, which will shed new light on the drug-loading field of Exo.

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Section: Discussionmentioning

confidence: 76%

SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats

Huang

et al. 2021

Stem Cell Res Ther

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“…Strategies to enhance exosome effectiveness as a therapeutic tool also consider manipulating endogenous exosome biodistribution to increase their local concentration in response to need. In this regard, Liu et al 48 designed antibody-conjugated magnetic nanoparticles that can be used as a vesicle shuttle, due to their ability to simultaneously capture circulating exosomes (CD63-antigen binding) and target injured cardiomyocytes (myosin-light chain antigen) in the infarcted area, in addition to facilitating the local release of the captured exosomes on the injured cardiac tissue. The applicability of this novel vesicle-shuttle approach as a strategy for therapy was demonstrated in rat and rabbit models of MI.…”

Section: Cell-to-cell Communication Via Exosomes and Non-coding Rnamentioning

confidence: 99%

Progress in cardiac research: from rebooting cardiac regeneration to a complete cell atlas of the heart

Davidson

Padró

Bollini

et al. 2021

Cardiovascular Research

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We review some of the important discoveries and advances made in basic and translational cardiac research in 2020. For example, in the field of myocardial infarction (MI), new aspects of autophagy and the importance of eosinophils were described. Novel approaches such as a glycocalyx mimetic were used to improve cardiac recovery following MI. The strategy of 3D bio-printing was shown to allow the fabrication of a chambered cardiac organoid. The benefit of combining tissue engineering with paracrine therapy to heal injured myocardium is discussed. We highlight the importance of cell-to cell communication, in particular the relevance of extracellular vesicles such as exosomes, which transport proteins, lipids, non-coding RNAs and mRNAs and actively contribute to angiogenesis and myocardial regeneration. In this rapidly growing field, new strategies were developed to stimulate the release of reparative exosomes in ischaemic myocardium. Single-cell sequencing technology is causing a revolution in the study of transcriptional expression at cellular resolution, revealing unanticipated heterogeneity within cardiomyocytes, pericytes and fibroblasts, and revealing a unique subpopulation of cardiac fibroblasts. Several studies demonstrated that exosome- and non-coding RNA-mediated approaches can enhance human induced pluripotent stem cell (iPSC) viability and differentiation into mature cardiomyocytes. Important details of the mitochondrial Ca2+ uniporter and its relevance were elucidated. Novel aspects of cancer therapeutic-induced cardiotoxicity were described, such as the novel circular RNA circITCH, which may lead to novel treatments. Finally, we provide some insights into the effects of SARS-CoV-2 on the heart.

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“…However, given that the mechanisms for regulating the exosome biodistribution are unclear, it is challengeable to achieve the manipulation of exosome biodistribution by regulating molecular signals. Recently, Liu et al 2 reported a vesicle shuttle (VS), which was composed of a ferroferric oxide core, a silica shell, and a stimuli‐cleavable poly(ethylene glycol) corona conjugated to two types of antibody (one against antigens on the exosomes of interest, and the other targeted to the recipient injured cells) 2 . They showed that the VS could effectively collect, transport, and release circulating exosomes to the designated areas inside the organism.…”

Section: Figurementioning

confidence: 99%

“…(iii) Release of the exosomes triggered by the infarct environment of pH <6.8, acidosis‐induced cleavage of hydrazone bonds, and shedding of the VS corona lead to the selective release of exosomes. Reproduced from Liu et al 2 …”

Section: Figurementioning

confidence: 99%

Manipulating endogenous exosome biodistribution for therapy

2021

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Treatment of infarcted heart tissue via the capture and local delivery of circulating exosomes through antibody-conjugated magnetic nanoparticles

Cited by 202 publications

References 51 publications

SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats

SiRNA in MSC-derived exosomes silences CTGF gene for locomotor recovery in spinal cord injury rats

Progress in cardiac research: from rebooting cardiac regeneration to a complete cell atlas of the heart

Manipulating endogenous exosome biodistribution for therapy

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