Developing an in vitro human epilepsy-on-a-chip model equipped with an intact blood-brain barrier for screening anti-epileptic drugs

Current epilepsy models are based on animal studies; however, it is proven that animal data does not correlate with the human data and that increases the failure rates of the therapeutics in clinical trials. Even though epilepsy is a widely seen chronic neurological disease, our knowledge on its genesis and progress on humans is limited, and we are failing to cure many refractory epileptic cases with current available drugs. In this project, we combine microfluidic devices with advanced stem cell technologies to develop a human epilepsy-on-a-chip model. This model will be the first in vitro human epilepsy model which includes a blood-brain barrier (BBB) component, enabling investigation of cellular interactions, as well as screening of antiepileptics that can cross the BBB.

The technology and knowledge developed during this project for designing, fabrication of the chips, and for differentiation of the stem cells will open new doors for further research. Furthermore, epilepsy-on-a-chip model will be the state-of-the-art in vitro human model to be used in drug development studies; also, it will be the best tool for studying cellular and mechanistic interactions during epileptogenesis. Therefore, the results of this project will potentially contribute to the development of new therapeutics which will ease many people’s lives who are suffering from epileptic seizures.

Finding innovative and alternative approaches to control the disease is of great importance to both Turkish and Iranian nations. This collaboration is thus of high importance as the Iranian team specializes in microfabrication and medical nanotechnology and the Turkish team are experts in stem cell biology and epilepsy. The combination of each team’s strengths will allow us to achieve a successful in vitro human epilepsy model that can be used to develop anti-epileptic drugs for patients.


Funding Agency TUBITAK MSRT
Proje Duration
  • Start day: 1 November 2021
  • End day: 1 May 2023
Team
  • PI: Nur Mustafaoglu, Sabanci University, Turkey
  • PI: Nasrollah Tabatabaei, Tehran University of Medical Sciences, Iran
  • Researcher: Mehmet Kaya, Koc University, Turkey
  • Researcher: Bulent Ahishali, Koc University, Turkey
  • Researcher: Vahid Bazargan, Tehran University, Iran
  • Researcher: Zahra Shiri, Royal Institute, Iran
  • Research Assistant: Neda Karami, Tehran University of Medical Sciences, Iran
  • PhD Student: Ecem Ayvaz, Koc University, Turkey
  • MSc Student: Eda Kus, Sabanci University, Turkey
Publications

  • Alireza Tajeddin, Nur Mustafaoglu, (2021). Design and Fabrication of Organ-on-Chips: Promises and Challenges. Micromachines, 12(12), p.1443. DOI: 10.3390/mi12121443

  • Eda Kus (2023). FUNCTIONAL NEURONS FROM HUMAN BONE MARROW DERIVED MESENCHYMAL STEM CELLS. MSc Thesis

  • Yomna Soliman (Leyla Yilmaz) (2023). HUMAN BONE MARROW-MESENCHYMAL STEM CELLS DIFFERENTIATION INTO BRAIN-LIKE ENDOTHELIAL CELLS. MSc Thesis

Outreach
News