State-of-the-art exosome loading and functionalization techniques for enhanced therapeutics: a review

Donoso‐Quezada, Javier; Ayala‐Mar, Sergio; González‐Valdez, José

doi:10.1080/07388551.2020.1785385

Cited by 78 publications

(62 citation statements)

References 111 publications

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“…Second, the therapeutic effect of MSC exosomes is reinforced by direct delivery of target molecules into MSC exosomes. A variety of insertion methods including passive loading, sonication, electroporation, extrusion, and light-induced loading have already been developed [136]. As we discussed above, anticancer drugs have been loaded into exosomes to achieve better clinical outcomes [104,105].…”

Section: Future Perspectives and Concluding Remarksmentioning

confidence: 99%

Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

Lee

Kang

2021

JCM

107

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Identification of the immunomodulatory and regenerative properties of mesenchymal stem cells (MSCs) have made them an attractive alternative therapeutic option for diseases with no effective treatment options. Numerous clinical trials have followed; however, issues such as infusional toxicity and cellular rejection have been reported. To address these problems associated with cell-based therapy, MSC exosome therapy was developed and has shown promising clinical outcomes. MSC exosomes are nanosized vesicles secreted from MSCs and represent a non-cellular therapeutic agent. MSC exosomes retain therapeutic features of the cells from which they originated including genetic material, lipids, and proteins. Similar to MSCs, exosomes can induce cell differentiation, immunoregulation, angiogenesis, and tumor suppression. MSC exosomes have therefore been employed in several experimental models and clinical studies. Here, we review the therapeutic potential of MSC-derived exosomes and summarize currently ongoing clinical trials according to disease type. In addition, we propose several functional enhancement strategies for the effective clinical application of MSC exosome therapy.

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Section: Future Perspectives and Concluding Remarksmentioning

confidence: 99%

Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

Lee

Kang

2021

JCM

107

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“…Brain-derived neurotrophic factor (BDNF) has been investigated enormously for conferring neuroprotection and anti-inflammatory properties. BDNF was encapsulated inside naïve exosomes and delivered to the brain against brain inflammation through IV administration to mice (Donoso-Quezada et al, 2020). MiR-206 knockdown exosomes attenuated early brain injury by upregulation of BDNF levels after exosome treatment (Zhao et al, 2019), which gives us an idea that bioengineering exosomes with BDNF could have a positive outcome for brain disorders, including stroke.…”

Section: Neurotrophic Factors (Ntfs)mentioning

confidence: 99%

Native and Bioengineered Exosomes for Ischemic Stroke Therapy

Khan

Pan

et al. 2021

Front. Cell Dev. Biol.

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Exosomes are natural cells-derived vesicles, which are at the forefront toward clinical success for various diseases, including cerebral ischemia. Exosomes mediate cell-to-cell communication in different brain cells during both physiological and pathological conditions. Exosomes are an extensively studied type of extracellular vesicle, which are considered to be the best alternative for stem cell–based therapy. They can be secreted by various cell types and have unique biological properties. Even though native exosomes have potential for ischemic stroke therapy, some undesirable features prevent their success in clinical applications, including a short half-life, poor targeting property, low concentration at the target site, rapid clearance from the lesion region, and inefficient payload. In this review, we highlight exosome trafficking and cellular uptake and survey the latest discoveries in the context of exosome research as the best fit for brain targeting owing to its natural brain-homing abilities. Furthermore, we overview the methods by which researchers have bioengineered exosomes (BioEng-Exo) for stroke therapy. Finally, we summarize studies in which exosomes were bioengineered by a third party for stroke recovery. This review provides up-to-date knowledge about the versatile nature of exosomes with a special focus on BioEng-Exo for ischemic stroke. Standard exosome bioengineering techniques are mandatory for the future and will lead exosomes toward clinical success for stroke therapy.

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“…For instance, electroporation was used to load miR-17-92 in MSCs to improve neuroprotective functions[ 45 ]. One of the major limitations of direct loading of exosomes using electroporation is the aggregation and fusion of exosomes[ 114 ]. Adding trehalose to the exosome solution has shown to improve the exosome colloidal stability and reduce aggregation[ 114 ].…”

Section: Improving Exosome Functions By Regulating Mirnas Via Bioengineering Approachesmentioning

confidence: 99%

Exosomal microRNAs from mesenchymal stem/stromal cells: Biology and applications in neuroprotection

Nasirishargh

Kumar

Ramasubramanian

et al. 2021

WJSC

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Mesenchymal stem/stromal cells (MSCs) are extensively studied as cell-therapy agents for neurological diseases. Recent studies consider exosomes secreted by MSCs as important mediators for MSCs’ neuroprotective functions. Exosomes transfer functional molecules including proteins, lipids, metabolites, DNAs, and coding and non-coding RNAs from MSCs to their target cells. Emerging evidence shows that exosomal microRNAs (miRNAs) play a key role in the neuroprotective properties of these exosomes by targeting several genes and regulating various biological processes. Multiple exosomal miRNAs have been identified to have neuroprotective effects by promoting neurogenesis, neurite remodeling and survival, and neuroplasticity. Thus, exosomal miRNAs have significant therapeutic potential for neurological disorders such as stroke, traumatic brain injury, and neuroinflammatory or neurodegenerative diseases and disorders. This review discusses the neuroprotective effects of selected miRNAs (miR-21, miR-17-92, miR-133, miR-138, miR-124, miR-30, miR146a, and miR-29b) and explores their mechanisms of action and applications for the treatment of various neurological disease and disorders. It also provides an overview of state-of-the-art bioengineering approaches for isolating exosomes, optimizing their yield and manipulating the miRNA content of their cargo to improve their therapeutic potential.

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State-of-the-art exosome loading and functionalization techniques for enhanced therapeutics: a review

Cited by 78 publications

References 111 publications

Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

Therapeutic Features and Updated Clinical Trials of Mesenchymal Stem Cell (MSC)-Derived Exosomes

Native and Bioengineered Exosomes for Ischemic Stroke Therapy

Exosomal microRNAs from mesenchymal stem/stromal cells: Biology and applications in neuroprotection

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