University of Twente Student Theses


Attenuating Inflammation by Modulation Microrna-155 Expression in Macrophages using Lipid Nanoparticles and Extracellular Vesicles

Türkal, Miranda (2022) Attenuating Inflammation by Modulation Microrna-155 Expression in Macrophages using Lipid Nanoparticles and Extracellular Vesicles.

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Abstract:Nonalcoholic fatty liver disease (NAFLD) is becoming a major health-related burden due to its growing prevalence worldwide. NAFLD comprises a wide range of liver diseases, including nonalcoholic steatohepatitis (NASH). NASH is characterized by liver cell damage, inflammation, hepatocellular ballooning, and an alternating range of fibrosis. Despite the wide distribution of NASH in populations, there is still a lack of treatment. Changes in the expression of microRNAs (miRNAs) are associated with different liver diseases, and an altered hepatic miRNA profile has been described in NASH. MiRNAs, small non-coding RNAs that can regulate post-transcriptional gene expression by binding target mRNAs. MiR-155 is considered the main inflammation modulator in the liver and its overexpression was observed in inflammatory macrophages upon LPS stimulation. The main objective of this project is to establish an antimiR-155 delivery platform to the liver macrophages to attenuate liver inflammation by reducing miR-155 and pro-inflammatory cytokine expressions. Lipid nanoparticles (LNPs) are one of the most advance non-viral delivery platforms for negatively charged nucleic acids. In this study, for the first time, we delivered antimiR-155 to inflammatory macrophages by using MC3 lipid-containing LNPs to alleviate the inflammatory response. We found reduced expression of TNFα and IL-6 along with miR-155 when 10mM antimiR-155 encapsulated LNPs were delivered to M1 macrophages. LNPs proved to be as efficient as commercially available transfection reagent HiPerFect while showing better tolerability in macrophages. As an alternative to LNPs, we used extracellular vesicles (EVs). Mesenchymal stem cells (MSCs)-derived exosomes show an inherent capacity to mitigate inflammation, and they are natural RNA carriers. For this project, for the first time, we used EVs derived from AMSCs transfected with antimiR-155. Even though pro-inflammatory cytokine TNFα expression did not change, we observed reduced IL-1β expression following increased anti-inflammatory markers.
Item Type:Essay (Master)
Faculty:TNW: Science and Technology
Subject:42 biology
Programme:Biomedical Engineering MSc (66226)
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