The Effect of Parent Cell Type on Small Extracellular Vesicle‐Derived Vehicle Functionality

Author:

Bheri Sruti1,Park Hyun‐Ji2,Hoffman Jessica R.3,Takaesu Felipe4,Davis Michael E.1345ORCID

Affiliation:

1. Wallace H. Coulter Department of Biomedical Engineering Georgia Institute of Technology & Emory University Atlanta GA 30332 USA

2. Department of Molecular Science and Technology Ajou University Suwon 16499 South Korea

3. Molecular & Systems Pharmacology Graduate Training Program Graduate Division of Biological & Biomedical Sciences Laney Graduate School Emory University Atlanta GA 30322 USA

4. Biochemistry Cell and Developmental Biology Graduate Training Program Graduate Division of Biological and Biomedical Sciences Laney Graduate School Emory University Atlanta GA 30332 USA

5. Children's Heart Research & Outcomes (HeRO) Center Children's Healthcare of Atlanta & Emory University Atlanta GA 30322 USA

Abstract

AbstractCell therapies involving c‐kit+ progenitor cells (CPCs) and mesenchymal stem cells (MSCs) have been actively studied for cardiac repair. The benefits of such therapies have more recently been attributed to the release of small extracellular vesicles (sEVs) from the parent cells. These sEVs are 30−180 nm vesicles containing protein/nucleic acid cargo encapsulated within an amphiphilic bilayer membrane. Despite their pro‐reparative effects, sEV composition and cargo loading is highly variable, making it challenging to develop robust therapies with sEVs. Synthetic alternatives have been developed to allow cargo modulation, including prior work from the laboratory, to design sEV‐like vehicles (ELVs). ELVs are synthesized from the sEV membrane but allow controlled cargo loading. It is previously shown that loading pro‐angiogenic miR‐126 into CPC‐derived ELVs significantly increases endothelial cell angiogenesis compared to CPC‐sEVs alone. Here, they expand on this work to design MSC‐derived ELVs  and study the role of the parent cell type on ELV composition and function. It is found that ELV origin does affect the ELV potency and that ELV membrane composition can affect outcomes. This study showcases the versatility of ELVs to be synthesized from different parent cells and highlights the importance of selecting ELV source cells based on the desired functional outcomes.

Funder

National Institutes of Health

National Heart, Lung, and Blood Institute

Publisher

Wiley

Subject

General Medicine

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