Date of Award

6-2018

Document Type

Thesis

Publisher

Santa Clara : Santa Clara University, 2018.

Department

Bioengineering

First Advisor

Bill Lu

Abstract

Rheumatoid arthritis (RA) is a widespread, debilitating autoimmune disease characterized by painful inflammation of the joints. Current treatments for RA are either ineffective, expensive, or have undesirable effects, such as an adverse immune response. To mitigate these effects, we have designed an exosome-based treatment for inflammation. We chose to utilize exosomes for their longer half-life in the body, better penetrative capacity, and biocompatibility, thus improving upon previous RA treatments. To do this, we created a stable cell line to produce exosomes modified at the surface to express a tumor necrosis factor receptor (TNFR), which possesses the ability to act as a decoy and soak up soluble tumor necrosis factor alpha (TNFα), a notable cytokine responsible for inducing inflammation. Exosomes were then harvested from this cell line and characterized with various imaging techniques to confirm that our desired modifications had been made. Then we tested the efficacy of our experiment in two models: direct treatment and coculture. Both models showed decreased levels of inflammation with the addition of our modified, treatment exosomes. If proven to be clinically successful, this therapy has the potential to be the first ever exosome decoy treatment.

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