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Title: The effect of imidazoquinoxaline agent EAPB0503 on the proliferation and differentiation potential of mesenchymal stem cells
Authors: Feghaly, Fouad Al
Advisors: Saliba, Jessica 
Issue Date: 2023
Background and purpose: The imidazoquinoxaline compound EAPB0503, an
analogue of imiquimod, exhibits anti-tumor properties against various types of leukemias.
However, the impact of EAPB0503 on non-cancerous cells, particularly mesenchymal stem
cells (MSCs), is not well-elucidated. Numerous studies highlight the interplay between MSCs
and leukemic cells within the bone marrow (BM) niche, influencing leukemogenesis and the
development of drug resistance. Building on previous research, this study investigates the
influence of EAPB0503 on MSCs derived from the bone marrow, specifically examining its
effects on proliferation and differentiation potential.
Method: In this research, the impact of EAPB0503 on an in vitro model of bone
marrow-derived mesenchymal stem cells (BM-MSCs) was examined. The assessment focused
on the cells' survival and their ability to differentiate into the osteogenic lineage after treatment
with EAPB0503, assessed through staining with alkaline phosphatase and Alizarin Red S.
Additionally, the study analyzed stemness and osteogenic markers in BM-MSCs, including N cadherin, connexin 43 (Cx43), alkaline phosphatase (ALP), NFκB, β-Catenin, and Snail, using
various techniques such as quantitative real-time PCR (qPCR), Western blot, and
Results: EAPB0503 at the concentration of 0.1 µM did not have any major effects on
cell proliferation and cell number and osteogenic differentiation at the phenotypic and at the
molecular level. However, at a higher concentration (0.5 µM), EAPB0503 reduced cell
proliferation and induced morphological changes. In addition, it compromised osteogenic
differentiation by downregulating osteogenic markers at transcript and protein levels
Conclusion: EAPB0503 does not seem to compromise healthy non-cancer cells,
namely BM-MSCs. This is of particular importance in leukemia treatment research; as
EAPB0503 has proven effective against leukemic cells and given the tight interplay between
hematopoietic cells (such as leukemic cells) and MSCs in the BM niche. More work is
underway to determine the effect of EAPB0503 in co-culture systems of leukemia cells and MSCs
Includes bibliographical references (p. [38-43])
Rights: This object is protected by copyright, and is made available here for research and educational purposes. Permission to reuse, publish, or reproduce the object beyond the personal and educational use exceptions must be obtained from the copyright holder
Ezproxy URL: Link to full text
Type: Thesis
Appears in Collections:UOB Theses and Projects

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