Graduate Studies

 

Date of Award

12-4-2023

Document Type

Dissertation

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Chemical and Biomolecular Engineering

First Advisor

Srivatsan Kidambi

Abstract

Liver is a complex organ but often underappreciated for its functions to remove toxins and fight infection in the body. Despite the ongoing prevalence of patients contracting chronic liver diseases, coupled with a global healthcare investment of approximately $70 billion, there is still no effective treatment for chronic liver diseases including alcoholic liver disease. The purpose of this dissertation was to understand the interactions of parenchymal and non-parenchymal liver cells in physiological and pathological like environments. This allowed us to recreate a healthy and the diseased microenvironments to observe the stages of the liver diseases development and apply appropriate treatments for the liver diseases. Substrate stiffness was used as a biomimetic approach to study the liver cells function and observe the differences of liver cells behavior when cultured on different microenvironments. Cell-cell communication, proteomic approach, and a novel drug delivery system were investigated to provide a potential treatment to chronic related liver diseases such as alcoholic liver disease. Hepatic stellate cells were found to enhance their functions in co-culture compared to a mono-culture system. EVs isolated from hepatocytes cultured on soft and stiff substrate revealed significant proteins involved in disease developments and were found to potentially serve as biomarkers for the early diagnosis for liver diseases. Treating with an antioxidant drug, vitamin E, the oxidative stress was found alleviated. Together, stiffness shows a plausible role in developing liver diseases and EVs isolated from hepatocytes cultured on various stiffnesses as well as lipid nanoparticles encapsulated with vitamin E should also be considered for the future treatment of alcoholic related liver diseases.

Comments

Copyright 2023, Youra Moeun

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