Title:
Engineering Small Extracellular Vesicle-Derived Vehicles Carrying Optimized microRNA for Cardiac Repair after Myocardial Infarction

dc.contributor.advisor Davis, Michael E.
dc.contributor.author Bheri, Sruti
dc.contributor.committeeMember Platt, Manu O.
dc.contributor.committeeMember Serpooshan, Vahid
dc.contributor.committeeMember Champion, Julie A.
dc.contributor.committeeMember Cho, Hee Cheol
dc.contributor.department Biomedical Engineering (Joint GT/Emory Department)
dc.date.accessioned 2023-05-18T17:48:28Z
dc.date.available 2023-05-18T17:48:28Z
dc.date.created 2023-05
dc.date.issued 2023-02-28
dc.date.submitted May 2023
dc.date.updated 2023-05-18T17:48:28Z
dc.description.abstract Myocardial infarction (MI) is one of the leading causes of morbidity and mortality worldwide. One promising therapy involves delivering small extracellular vesicles (sEVs). These sEVs are 30-150 nm vesicles containing protein and/or nuclear cargo. Despite their reparative potential, sEV therapies have several issues due to their cellular origin, including variable sEV yield and uncontrolled and low-density cargo encapsulation. Synthetic sEV-mimics have been developed which allow optimized cargo loading but these have high toxicity, compromised membranes and poor uptake. Therefore, there is a need for cell-free vehicles with sEV-like membrane and uptake, which allow delivery of customized cargo. To address these needs, the aim of this study was (1) to develop an sEV-like vehicle (ELV) with select microRNA (miR) cargo for cardiac repair and (2) to understand the role of the sEV membrane on vesicle uptake and ELV functionality. We hypothesized that ELVs comprised of an sEV membrane and loaded with miR cargo will improve cardiac tissue repair after MI compared to sEVs alone and that membrane composition will affect ELV functionality. The ELVs were loaded with miR-126, an endothelial marker, and when administered to cardiac endothelial cells, improved angiogenesis compared to sEV treatment. We then injected miR-126+ELVs into a rat model of ischemia-reperfusion wherein the ELVs reduced infarct size, fibrosis and hypertrophy and increased angiogenic parameters. We then assessed the relationship between sEV membrane composition and uptake mechanism finding that sEV origin affects both composition and uptake. We tested this by engineering miR-126+ELVs from two cell types and found differences in their angiogenic and proliferative capacity. Taken together, this study demonstrates the value of engineering vehicles with sEV membranes and their potential to deliver selective cargo for cardiac repair after MI.
dc.description.degree Ph.D.
dc.format.mimetype application/pdf
dc.identifier.uri https://hdl.handle.net/1853/71964
dc.language.iso en_US
dc.publisher Georgia Institute of Technology
dc.subject Myocardial Infarction
dc.subject Extracellular vesicles
dc.subject Exosomes
dc.subject Engineered vesicles
dc.subject Liposome
dc.subject Cardiac repair
dc.subject C-kit+ progenitor cells
dc.subject microRNA 126
dc.subject Extracellular vesicle uptake
dc.subject Ischemia reperfusion
dc.subject Rat heart failure
dc.title Engineering Small Extracellular Vesicle-Derived Vehicles Carrying Optimized microRNA for Cardiac Repair after Myocardial Infarction
dc.type Text
dc.type.genre Dissertation
dspace.entity.type Publication
local.contributor.advisor Davis, Michael E.
local.contributor.corporatename College of Engineering
local.contributor.corporatename Wallace H. Coulter Department of Biomedical Engineering
relation.isAdvisorOfPublication fab83195-e1b0-4b5e-933d-5b97a14b945a
relation.isOrgUnitOfPublication 7c022d60-21d5-497c-b552-95e489a06569
relation.isOrgUnitOfPublication da59be3c-3d0a-41da-91b9-ebe2ecc83b66
thesis.degree.level Doctoral
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