Cardiac-specific delivery by cardiac tissue-targeting peptide-expressing exosomes

Kim, Hyoeun; Yun, Nuri; Mun, Dasom; Kang, Ji; Lee, Seung‐Hyun; Park, Hyelim; Joung, Boyoung

doi:10.1016/j.bbrc.2018.03.227

Cited by 123 publications

(85 citation statements)

References 26 publications

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“…It is important to bear in mind that not all cardiovascular patients may be eligible for acute in situ treatment requiring either percutaneous coronary intervention/angioplasty or collateral cardiac surgery; therefore, there is an increasing need for optimizing EV cardiac-specific homing for future cell-free paracrine therapy. Several studies have been lately reported suggesting alternative strategies to functionalise EVs for more accurate targeting of the damaged heart [220,221]. These include: lentiviral vector-based engineering of secreting cells to upregulate the expression of cardiomyocyte-specific binding peptides fused to the murine transmembrane protein Lamp2b, in order to enrich the targeting epitope on the exosomal surface [222]; overexpression of exosomal CXCR4 to push their bioavailability towards the ischaemic heart [156]; membrane anchoring systems to directly dock tissue-specific antibodies or homing antigens on the EV surface [223,224].…”

Section: Looking For the Right Address: Improving Ev Cardiac Tropismmentioning

confidence: 99%

Message in a Bottle: Upgrading Cardiac Repair into Rejuvenation

Balbi

Costa

Barile

2020

Cells

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Ischaemic cardiac disease is associated with a loss of cardiomyocytes and an intrinsic lack of myocardial renewal. Recent work has shown that the heart retains limited cardiomyocyte proliferation, which remains inefficient when facing pathological conditions. While broadly active in the neonatal mammalian heart, this mechanism becomes quiescent soon after birth, suggesting loss of regenerative potential with maturation into adulthood. A key question is whether this temporary regenerative window can be enhanced via appropriate stimulation and further extended. Recently the search for novel therapeutic approaches for heart disease has centred on stem cell biology. The "paracrine effect" has been proposed as a promising strategy to boost endogenous reparative and regenerative mechanisms from within the cardiac tissue by exploiting the modulatory potential of soluble stem cell-secreted factors. As such, growing interest has been specifically addressed towards stem/progenitor cell-secreted extracellular vesicles (EVs), which can be easily isolated in vitro from cell-conditioned medium. This review will provide a comprehensive overview of the current paradigm on cardiac repair and regeneration, with a specific focus on the role and mechanism(s) of paracrine action of EVs from cardiac stromal progenitors as compared to exogenous stem cells in order to discuss the optimal choice for future therapy. In addition, the challenges to overcoming translational EV biology from bench to bedside for future cardiac regenerative medicine will be discussed.

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Section: Looking For the Right Address: Improving Ev Cardiac Tropismmentioning

confidence: 99%

Message in a Bottle: Upgrading Cardiac Repair into Rejuvenation

Balbi

Costa

Barile

2020

Cells

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“…Overall, cancer-targeting EVs showed no evidence of general toxicity while effectively delivering chemotherapeutics to solid tumors. Similarly, Kim et al [ 181 ] exploited the Lamp2b protein fused with cardiac-targeting peptide (CTP; APWHLSSWYSRT) to target HEK293-derived EVs into the heart. In vitro studies indicated increased uptake of CTP-modified EVs by cardiomyocytes although HEK293 cells were transfected by CTP-modified and unmodified EVs with similar efficiency.…”

Section: Engineering the Surface Of Evs For Improved And Targeted mentioning

confidence: 99%

Gene Editing by Extracellular Vesicles

Kostyushev

Kostyusheva

Brezgin

et al. 2020

IJMS

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CRISPR/Cas technologies have advanced dramatically in recent years. Many different systems with new properties have been characterized and a plethora of hybrid CRISPR/Cas systems able to modify the epigenome, regulate transcription, and correct mutations in DNA and RNA have been devised. However, practical application of CRISPR/Cas systems is severely limited by the lack of effective delivery tools. In this review, recent advances in developing vehicles for the delivery of CRISPR/Cas in the form of ribonucleoprotein complexes are outlined. Most importantly, we emphasize the use of extracellular vesicles (EVs) for CRISPR/Cas delivery and describe their unique properties: biocompatibility, safety, capacity for rational design, and ability to cross biological barriers. Available molecular tools that enable loading of desired protein and/or RNA cargo into the vesicles in a controllable manner and shape the surface of EVs for targeted delivery into specific tissues (e.g., using targeting ligands, peptides, or nanobodies) are discussed. Opportunities for both endogenous (intracellular production of CRISPR/Cas) and exogenous (post-production) loading of EVs are presented.

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“…This will allow for the recurrent administration of therapeutic exosomes, i.e., as required to achieve the therapeutic goal, without needing to administer immunosuppressive drugs in parallel. Third, exosomes are released with membrane-bound proteins that can be easily engineered to target a given tissue, including bone, and be incorporated into its cells [ 50 , 51 ]. Poor engraftment within the targeted tissue and accumulation of transplanted cells in nontargeted organs, mostly the lungs, are also issues in cell-based therapies [ 52 , 53 ].…”

Section: Clinical Applicationsmentioning

confidence: 99%

Preparing the Bone Tissue Regeneration Ground by Exosomes: From Diagnosis to Therapy

2020

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Bone tissue engineering employs acellular scaffolds or scaffolds, along with cells and growth factors, to provide the mechanical support needed, as well as serve as a delivery vehicle for bioactive molecules to the injury sites. As tissue engineering continues to evolve, it has integrated two emerging fields: stem cells and nanotechnology. A paracrine factor that is found to be responsible for the major regenerative effect in stem cell transplantation is an extracellular vesicle called an ‘exosome’. Recent advances in nanotechnology have allowed the ‘exosome’ to be distinguished from other extracellular vesicles and be polymerized into a well-defined concept. Scientists are now investigating exosome uses in clinical applications. For bone-related diseases, exosomes are being explored as biomarkers for different bone pathologies. They are also being explored as a therapeutic agent where progenitor cell-derived exosomes are used to regenerate damaged bone tissue. In addition, exosomes are being tested as immune modulators for bone tissue inflammation, and finally as a delivery vehicle for therapeutic agents. This review discusses recently published literature on the clinical utilization of exosomes in bone-related applications and the correlated advantages. A particular focus will be placed on the potential utilization of regenerative cell-derived exosomes as a natural biomaterial for tissue regeneration.

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Cardiac-specific delivery by cardiac tissue-targeting peptide-expressing exosomes

Cited by 123 publications

References 26 publications

Message in a Bottle: Upgrading Cardiac Repair into Rejuvenation

Message in a Bottle: Upgrading Cardiac Repair into Rejuvenation

Gene Editing by Extracellular Vesicles

Preparing the Bone Tissue Regeneration Ground by Exosomes: From Diagnosis to Therapy

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