Development of human in vivo-like cellular systems by using induced pluripotent stem cell-derived organoids and organ-on-a-chips as an alternative to mouse models to investigate environmental exposure to toxic substances


Yazıcı D., Pat Y., Ardıçlı S., Akdiş C.

Diğer Ülkelerden Üniversiteler Tarafından Desteklenmiş Proje, 2024 - 2025

  • Proje Türü: Diğer Ülkelerden Üniversiteler Tarafından Desteklenmiş Proje
  • Başlama Tarihi: Nisan 2024
  • Bitiş Tarihi: Nisan 2025

Proje Özeti

-        The prevalence of allergic and autoimmune diseases, including peanut allergy, has risen significantly in recent decades, particularly in Westernized countries. While the exact cause of peanut allergy remains unclear, food processing methods may play a role in increasing antigenicity and contributing to the rise in allergies.

-        This project aims to investigate the potential role of food emulsifiers, commonly used in peanut butter production since the 2000s, on epithelial cells, causing inflammation, and damaging intestinal epithelial barrier integrity, which may lead to peanut allergy.

Three major objectives guide the project:

-        Combining induced pluripotent stem cell (iPSC)-derived intestine organoids and organ-on-a-chips to mimic the in vivo environment, demonstrating the activation and regulation of epithelial cells in response to environmental toxic substances.

-        Studying three commonly used emulsifiers in peanut butter – soy lecithin, diacetyl tartaric acid ester of mono- and diglycerides (DATEM), and palm oil – to assess their impact on epithelial cell activation and barrier strength, both individually and in combination with type 2 immune response-related cytokines.

-        Identifying the molecular mechanisms of action of emulsifiers on intestinal epithelial cells through transcriptomics, proteomics studies, and inhibition studies using CRISPR/Cas9 and siRNA technologies.

The findings will guide strategies to reduce related diseases, control substance doses, develop less-toxic products, and explore new therapeutic approaches. Moreover, the research aligns with the principles of the 3Rs (Replacement, Reduction, Refinement), potentially reducing the need for animal research. Since it uses highly in vivo relevant in vitro models such as organoids and organ-on-a-chips rather than animal models.