Keywords

Stem Cells; MSC-Exos; Doxorubicin; Cardiotoxicity; Pyroptosis; Inflammation

Abstract

Doxorubicin (DOX) is an incessantly used chemotherapeutic drug that can cause detrimental dose-dependent effects such as cardiotoxicity and congestive heart failure. Studies have focused on therapeutic strategies such as exosomes derived from embryonic stem cell (ES-Exos) and antioxidants for example resveratrol; however, the function of mesenchymal stem cell-derived exosomes (MSC-Exos) have never been examined in DOX-induced pyroptosis. MSC-Exos maintains the therapeutic potential of exosome therapy without the ethical concerns. Hence, the current study focuses on determining whether MSC-Exos has the potential to ameliorate inflammation-induced cell death pyroptosis in our established in vitro DOX-induced cardiotoxicity (DIC) model. Rat embryonic cardiomyocytes (H9c2) were first exposed to DOX to stimulate pyroptosis, followed by subsequent treatment with MSC-Exos, with further analysis performed through immunocytochemistry, western blotting, and RT-PCR. We evaluated the therapeutic potential of MSC-Exos by investigating the pyroptotic initiator HMGB1 which binds to TLR4 resulting in the formation of the NLRP3 inflammasome that initiates pyroptosis by activating the pyroptotic markers, caspase-1, IL-1β and IL-18, and the pyroptotic executioner GSDMD. Our data depicted that treatment with MSC-Exos significantly (p

Completion Date

2023

Semester

Fall

Committee Chair

Singla, Dinender

Degree

Master of Science (M.S.)

College

College of Medicine

Department

Burnett School of Biomedical Sciences

Degree Program

Biotechnology

Format

application/pdf

Identifier

DP0028003

URL

https://purls.library.ucf.edu/go/DP0028003

Language

English

Release Date

December 2028

Length of Campus-only Access

5 years

Access Status

Masters Thesis (Campus-only Access)

Campus Location

Orlando (Main) Campus

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Restricted to the UCF community until December 2028; it will then be open access.

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