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Full text release has been delayed at the author's request until December 19, 2027

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Engineering Extracellular Vesicles for Therapeutic Applications

Salazar Puerta, Ana Isabel
http://orcid.org/0000-0003-4954-6226
http://rave.ohiolink.edu/etdc/view?acc_num=osu1669730479934026

Abstract Details

2022, Doctor of Philosophy, Ohio State University, Biomedical Engineering.
Extracellular vesicles (EVs) are naturally derived lipid membrane vesicles that are released by different cell types into the extracellular environment, and they play a crucial role in cell-to-cell communication and mirror specific molecular cues characteristic of the donor cell. EVs have emerged as promising delivery vehicles for therapeutic applications, due to their long-term stability in biofluids and systemic circulation, ability to penetrate biological barriers (e.g., cytoplasmatic membrane), low immunogenicity, exceptional biocompatibility, and ability to transport and deliver a variety of therapeutic agents. Therefore, while naturally derived EVs have shown to favor targeting towards specific cells/tissues, studies have evaluated the ability to introduce extrinsic properties to EVs such as surface modification with specific targeting ligands to enhance preferential EV uptake, as well as tailoring of their molecular cargo, maximizing thus therapeutic efficiency. The first chapter of this dissertation discusses the properties of these natural carriers and the different strategies that have been used to produce engineered EVs. The second chapter illustrates the development and implementation of engineered EVs as novel non-viral gene delivery systems to deliver anti-inflammatory molecular cargo with a therapeutic effect on inflammatory conditions. Similarly, the following chapter describes the fabrication of engineered EVs loaded with anti-inflammatory cargo and functionalized on the surface with targeting ligands to selectively deliver therapeutic payloads to the inflamed lung with the ability to reduce inflammation both in vitro and in vivo. The last chapter describes the development and implementation of designer EVs loaded with reprogramming transcription factors that can be effectively transferred and overexpressed by aortic valve tissue from patients that underwent valve replacement due to aortic stenosis, and their ability to induce cell reprogramming of endothelial cells towards a macrophage-like phenotype. Finally, the appendixes show the inherent tropism capabilities of EVs to target specific cells/tissues when derived from the same cell of origin, as well as the enhanced tropism that can be achieved when introducing specific targeting ligands to target specific cell populations such as Schwann cells. Finally, at the end of this dissertation, we present the summarizing conclusions and future directions for the aggregates of all chapters.
Natalia Higuita-Castro (Advisor)
Devina Walter (Committee Member)
Daniel Gallego-Perez (Committee Member)
285 p.
Biomedical Engineering
Engineered extracellular vesicles, nonviral gene delivery, anti-inflammatory extracellular vesicles, novel nanocarriers, lung injury, inflammatory-related diseases, cardiovascular diseases

Recommended Citations

Citations

  • Salazar Puerta, A. I. (2022). Engineering Extracellular Vesicles for Therapeutic Applications [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1669730479934026

    APA Style (7th edition)

  • Salazar Puerta, Ana. Engineering Extracellular Vesicles for Therapeutic Applications. 2022. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1669730479934026.

    MLA Style (8th edition)

  • Salazar Puerta, Ana. "Engineering Extracellular Vesicles for Therapeutic Applications." Doctoral dissertation, Ohio State University, 2022. http://rave.ohiolink.edu/etdc/view?acc_num=osu1669730479934026

    Chicago Manual of Style (17th edition)

osu1669730479934026
© 2022, some rights reserved.Creative Commons License Engineering Extracellular Vesicles for Therapeutic Applications by Ana Isabel Salazar Puerta is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. Based on a work at etd.ohiolink.edu.
This open access ETD is published by The Ohio State University and OhioLINK.