Dataset Information

Hybrid extracellular vesicles-liposome incorporated advanced bioink to deliver microRNA.

ABSTRACT: In additive manufacturing, bioink formulations govern strategies to engineer 3D living tissues that mimic the complex architectures and functions of native tissues for successful tissue regeneration. Conventional 3D-printed tissues are limited in their ability to alter the fate of laden cells. Specifically, the efficient delivery of gene expression regulators (i.e. microRNAs (miRNAs)) to cells in bioprinted tissues has remained largely elusive. In this study, we explored the inclusion of extracellular vesicles (EVs), naturally occurring nanovesicles (NVs), into bioinks to resolve this challenge. EVs show excellent biocompatibility, rapid endocytosis, and low immunogenicity, which lead to the efficient delivery of miRNAs without measurable cytotoxicity. EVs were fused with liposomes to prolong and control their release by altering their physical interaction with the bioink. Hybrid EVs-liposome (hEL) NVs were embedded in gelatin-based hydrogels to create bioinks that could efficiently encapsulate and deliver miRNAs at the target site in a controlled and sustained manner. The regulation of cells' gene expression in a 3D bioprinted matrix was achieved using the hELs-laden bioink as a precursor for excellent shape fidelity and high cell viability constructs. Novel regulatory factors-loaded bioinks will expedite the translation of new bioprinting applications in the tissue engineering field.

SUBMITTER: Elkhoury K

PROVIDER: S-EPMC9594995 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Hybrid extracellular vesicles-liposome incorporated advanced bioink to deliver microRNA.

Elkhoury Kamil K Chen Mo M Koçak Polen P Enciso-Martínez Eduardo E Bassous Nicole Joy NJ Lee Myung Chul MC Byambaa Batzaya B Rezaei Zahra Z Li Yang Y Ubina López María Elizabeth ME Gurian Melvin M Sobahi Nebras N Hussain Mohammad Asif MA Sanchez-Gonzalez Laura L Leijten Jeroen J Hassan Shabir S Arab-Tehrany Elmira E Ward Jennifer Ellis JE Shin Su Ryon SR

Biofabrication 20220819 4

In additive manufacturing, bioink formulations govern strategies to engineer 3D living tissues that mimic the complex architectures and functions of native tissues for successful tissue regeneration. Conventional 3D-printed tissues are limited in their ability to alter the fate of laden cells. Specifically, the efficient delivery of gene expression regulators (i.e. microRNAs (miRNAs)) to cells in bioprinted tissues has remained largely elusive. In this study, we explored the inclusion of extrace ...[more]

PMID: 35917808

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Project description:Clustered regularly interspaced palindromic repeats (CRISPR) is a gene editing tool with tremendous therapeutic potential. Recently, ribonucleoprotein (RNP) complex-based CRISPR systems have gained momentum due to their reduction of off-target editing. This has coincided with the emergence of extracellular vesicles (EVs) as a therapeutic delivery vehicle due to its low immunogenicity and high capacity for manipulation. EVs are cell-derived membranous nanoparticles which mediate the intercellular transfer of molecular components. Current technologies achieve CRISPR RNP encapsulation into EVs through EVs biogenesis, thereby avoiding unnecessary physical, chemical or biological manipulations to the vesicles directly. Herein, we identify sixteen EVs-based CRISPR RNP encapsulation strategies, each with distinct genetic features to encapsulate CRISPR RNP. According to the molecular mechanism facilitating the encapsulation process, there are six strategies of encapsulating Cas9 RNP into virus-like particles based on genetic fusion, seven into EVs based on protein tethering, and three based on sgRNA-coupled encapsulation. Additionally, the incorporation of a targeting moiety to the EVs membrane surface through EVs biogenesis confers tropism and increases delivery efficiency to specific cell types. The targeting moieties include viral envelope proteins, recombinant proteins containing a ligand peptide, single-chain fragment variable (scFv) antibodies, and integrins. However, current strategies still have a number of limitations which prevent their use in clinical trials. Among those, the incorporation of viral proteins for encapsulation of Cas9 RNP have raised issues of biocompatibility due to host immune response. Future studies should focus on genetically engineering the EVs without viral proteins, enhancing EVs delivery specificity, and promoting EVs-based homology directed repair. Nevertheless, the integration of CRISPR RNP encapsulation and tropism technologies will provide strategies for the EVs-based delivery of CRISPR RNP in gene therapy and disease treatment.

Project description:BackgroundSevere cases of COVID-19 are characterized by an excessive presence of neutrophils. Neutrophil extracellular traps (NETs), released by activated neutrophils due to SARS-CoV-2 infection, contribute to lung epithelial cell death and are key drivers in COVID-19-associated immunothrombosis. However, the mechanism underlying NET formation in COVID-19 remain unclear.MethodsExtracellular vesicles (EVs) were isolated from the serum of COVID-19 patients and healthy volunteers, while neutrophils were isolated from blood samples of healthy volunteers. Neutrophils were treated with EVs, and the formation of NETs was observed. To identify the components responsible for the COVID-19-EVs-induced NET formation, we analyzed the expression profiles of microRNA (miRNAs) in COVID-19-EVs. We identified eight highly expressed miRNAs in COVID-19-EVs and explored their potential roles in COVID-19-EVs-mediated NET formation. Additionally, we explored the role of miR-20b-5p in COVID-19-EVs-induced NET formation.ResultsIn this study, we demonstrate that patients with COVID-19 have a higher concentration of serum EVs (COVID-19-EVs) than healthy controls (Normal-EVs). We also found that COVID-19-EVs are internalized by neutrophils to induced NET formation. Through comprehensive miRNA profiling of COVID-19-EVs versus Normal-EVs, we identified 78 differentially expressed miRNAs, with 27 of these being upregulated and 51 being downregulated. Subsequently, we discovered that COVID-19-EVs that were highly abundant with certain miRNAs promote NET formation. Specifically, miR-20b-5p was found to be the strongest inducer of NET formation of the identified miRNAs. Inhibition of miR-20b-5p resulted in a significant decrease in COVID-19-EVs-mediated induction of NET formation.ConclusionHerein, we reveal a previously unknown role of COVID-19-EVs in NET formation, which contributes to COVID-19 progression. This study suggests that miR-20b-5p may serve as a potential therapeutic target for COVID-19 treatment.

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Hybrid extracellular vesicles-liposome incorporated advanced bioink to deliver microRNA.

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Hybrid extracellular vesicles-liposome incorporated advanced bioink to deliver microRNA.

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