PhD Scientific Days 2025

Pathological and Oncological Sciences I.

Investigation of the immunoregulatory effects of vesicles derived from genetically modified embryonic stem cells

Name of the presenter

Nagy Boglárka

Institute/workplace of the presenter

Genetics, Cell-, and Immunbiology Institute

Authors

Boglárka Nagy¹, Luigi Menna¹, Kristóf Csont¹, Nóra Fekete¹, Xabier Osteikoetxea¹, Adrienn Szabó¹, Angéla Takács¹, Edit Buzás¹, Hargita Hegyesi¹

1: Genetics, Cell-, and Immunbiology Institute

Text of the abstract

Investigation of the Immunoregulatory Effects of Vesicles Derived from Genetically Modified Embryonic Stem Cells

Introduction:
Extracellular vesicles (EVs) from embryonic stem cells are emerging as promising therapeutic tools due to their ability to deliver bioactive molecules—such as proteins, lipids, and RNAs—targetedly. They promote regeneration, reduce inflammation, and present fewer ethical and immunological concerns than direct stem cell therapies.
Aims:
This study examined how a mouse embryonic stem cell line, stably transfected with eight genes, and its derived EVs affect peripheral mononuclear cell populations. The hypothesis was that these modified cells and their EVs could modulate immune responses and serve as potential therapeutic agents.
Methods:
The NT2 cell line expresses seven immunoregulatory proteins and a thymidine kinase gene for selective elimination. EVs were isolated from conditioned medium via differential centrifugation. Vesicle size and concentration were analyzed by nanoparticle tracking, and surface markers identified by flow cytometry. Immunomodulatory effects were assessed in vitro and in vivo by measuring CD4+, CD8+ T cells, B cells, and monocytes.
Result:
NT2-derived EVs expressed Annexin V, CD81, and the immunoregulatory molecules PDL-1, CD47, and CD200—absent in control EVs. NT2 cells, both in direct and indirect co-culture, reduced activated T cell numbers. In vivo, teratomas from NT2 cells significantly decreased CD4+, CD8+ T cells, and monocytes in peripheral blood.
Conclusion:
EVs from genetically modified embryonic stem cells carry key immunoregulatory molecules and reduce immune cell counts, indicating their potential as future tools in immunomodulatory therapy.
Funding: TKP2021-EGA-23. This study was also supported by the grants RRF-2.3.121-2022-00003 (National Cardiovascular Laboratory Program) and 2019-2.1.7-ERA-NET-2021-00015. The project has received funding from the EU’s Horizon 2020 Research and Innovation Programme under grant agreement No. 739593 and the NKFIH Advanced grant 150767.


E-mail: nagyboglarka23@gmail.com
Name of the University: Semmelweis University
Name of the Supervisor: dr. Hegyesi Hargita
For me it is preferred to be presented as an oral presentation (in English).