Engineering Cardiac Small Extracellular Vesicle-Derived Vehicles with Thin-Film Hydration for Customized microRNA Loading

Cell therapies for myocardial infarction, including cardiac ckit+ progenitor cell (CPC) therapies, have been promising, with clinical trials underway. Recently, paracrine signaling, specifically through small extracellular vesicle (sEV) release, was implicated in cell-based cardiac repair. sEVs carr...

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Autores principales:	Sruti Bheri, Brandon P. Kassouf, Hyun-Ji Park, Jessica R. Hoffman, Michael E. Davis
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	extracellular vesicle vesicle engineering exosome cardiac ckit+ progenitor cell cardiac repair thin-film hydration Diseases of the circulatory (Cardiovascular) system RC666-701
Acceso en línea:	https://doaj.org/article/424be981ee8249c899480c50ab1d6afd
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spelling	oai:doaj.org-article:424be981ee8249c899480c50ab1d6afd2021-11-25T18:00:11ZEngineering Cardiac Small Extracellular Vesicle-Derived Vehicles with Thin-Film Hydration for Customized microRNA Loading10.3390/jcdd81101352308-3425https://doaj.org/article/424be981ee8249c899480c50ab1d6afd2021-10-01T00:00:00Zhttps://www.mdpi.com/2308-3425/8/11/135https://doaj.org/toc/2308-3425Cell therapies for myocardial infarction, including cardiac ckit+ progenitor cell (CPC) therapies, have been promising, with clinical trials underway. Recently, paracrine signaling, specifically through small extracellular vesicle (sEV) release, was implicated in cell-based cardiac repair. sEVs carry cardioprotective cargo, including microRNA (miRNA), within a complex membrane and improve cardiac outcomes similar to that of their parent cells. However, miRNA loading efficiency is low, and sEV yield and cargo composition vary with parent cell conditions, minimizing sEV potency. Synthetic mimics allow for cargo-loading control but consist of much simpler membranes, often suffering from high immunogenicity and poor stability. Here, we aim to combine the benefits of sEVs and synthetic mimics to develop sEV-like vesicles (ELVs) with customized cargo loading. We developed a modified thin-film hydration (TFH) mechanism to engineer ELVs from CPC-derived sEVs with pro-angiogenic miR-126 encapsulated. Characterization shows miR-126+ ELVs are similar in size and structure to sEVs. Upon administration to cardiac endothelial cells (CECs), ELV uptake is similar to sEVs too. Further, when functionally validated with a CEC tube formation assay, ELVs significantly improve tube formation parameters compared to sEVs. This study shows TFH-ELVs synthesized from sEVs allow for select miRNA loading and can improve in vitro cardiac outcomes.Sruti BheriBrandon P. KassoufHyun-Ji ParkJessica R. HoffmanMichael E. DavisMDPI AGarticleextracellular vesiclevesicle engineeringexosomecardiac ckit+ progenitor cellcardiac repairthin-film hydrationDiseases of the circulatory (Cardiovascular) systemRC666-701ENJournal of Cardiovascular Development and Disease, Vol 8, Iss 135, p 135 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	extracellular vesicle vesicle engineering exosome cardiac ckit+ progenitor cell cardiac repair thin-film hydration Diseases of the circulatory (Cardiovascular) system RC666-701
spellingShingle	extracellular vesicle vesicle engineering exosome cardiac ckit+ progenitor cell cardiac repair thin-film hydration Diseases of the circulatory (Cardiovascular) system RC666-701 Sruti Bheri Brandon P. Kassouf Hyun-Ji Park Jessica R. Hoffman Michael E. Davis Engineering Cardiac Small Extracellular Vesicle-Derived Vehicles with Thin-Film Hydration for Customized microRNA Loading
description	Cell therapies for myocardial infarction, including cardiac ckit+ progenitor cell (CPC) therapies, have been promising, with clinical trials underway. Recently, paracrine signaling, specifically through small extracellular vesicle (sEV) release, was implicated in cell-based cardiac repair. sEVs carry cardioprotective cargo, including microRNA (miRNA), within a complex membrane and improve cardiac outcomes similar to that of their parent cells. However, miRNA loading efficiency is low, and sEV yield and cargo composition vary with parent cell conditions, minimizing sEV potency. Synthetic mimics allow for cargo-loading control but consist of much simpler membranes, often suffering from high immunogenicity and poor stability. Here, we aim to combine the benefits of sEVs and synthetic mimics to develop sEV-like vesicles (ELVs) with customized cargo loading. We developed a modified thin-film hydration (TFH) mechanism to engineer ELVs from CPC-derived sEVs with pro-angiogenic miR-126 encapsulated. Characterization shows miR-126+ ELVs are similar in size and structure to sEVs. Upon administration to cardiac endothelial cells (CECs), ELV uptake is similar to sEVs too. Further, when functionally validated with a CEC tube formation assay, ELVs significantly improve tube formation parameters compared to sEVs. This study shows TFH-ELVs synthesized from sEVs allow for select miRNA loading and can improve in vitro cardiac outcomes.
format	article
author	Sruti Bheri Brandon P. Kassouf Hyun-Ji Park Jessica R. Hoffman Michael E. Davis
author_facet	Sruti Bheri Brandon P. Kassouf Hyun-Ji Park Jessica R. Hoffman Michael E. Davis
author_sort	Sruti Bheri
title	Engineering Cardiac Small Extracellular Vesicle-Derived Vehicles with Thin-Film Hydration for Customized microRNA Loading
title_short	Engineering Cardiac Small Extracellular Vesicle-Derived Vehicles with Thin-Film Hydration for Customized microRNA Loading
title_full	Engineering Cardiac Small Extracellular Vesicle-Derived Vehicles with Thin-Film Hydration for Customized microRNA Loading
title_fullStr	Engineering Cardiac Small Extracellular Vesicle-Derived Vehicles with Thin-Film Hydration for Customized microRNA Loading
title_full_unstemmed	Engineering Cardiac Small Extracellular Vesicle-Derived Vehicles with Thin-Film Hydration for Customized microRNA Loading
title_sort	engineering cardiac small extracellular vesicle-derived vehicles with thin-film hydration for customized microrna loading
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/424be981ee8249c899480c50ab1d6afd
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Engineering Cardiac Small Extracellular Vesicle-Derived Vehicles with Thin-Film Hydration for Customized microRNA Loading

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