Pathological and Oncological Sciences 1.
Ms. Nagy, Boglárka
MBAKEN
Institute of Genetics, Cell- and Immunobiology
06302033005
nagyboglarka23@gmail.com
Analysis of immunomodulatory effects exerted by vesicles derived from genetically modified embryonic stem cells
Boglárka Nagy1, Luigi Menna1, Kristóf Csont1, Nóra Fekete1, Xabier Osteikoetxea1, Adrienn Szabó1, Angéla Takács1, Edit Buzás1, Hargita Hegyesi1
1: Institute of Genetics, Cell- and Immunobiology
Szóbeli
Pathological and Oncological Sciences 1.
English
Pathological and Oncological Sciences
Introduction:
Extracellular vesicles (EVs) derived from embryonic stem cells (ESCs) are emerging as promising agents for modulating intercellular communication and immune responses. Compared with stem cell transplantation, EV-based therapies offer reduced immunogenicity, improved safety, and fewer ethical concerns. ESC lines can be engineered to produce EVs enriched with immunoregulatory molecules, providing a controllable platform for cell-free immunotherapy.
Aims:
This study investigated the immunomodulatory potential of a genetically modified mouse ESC line (NT2), focusing on the in vitro and in vivo effects of its EVs.
Method:
NT2 cells express seven immunoregulatory proteins (PD-L1, CD47, CD200, SerpinB9, MFGE8, CCL21, H2-M3) and the HSV-TK suicide gene enabling controlled elimination via ganciclovir treatment. EVs were isolated using differential centrifugation and they were characterized by nanoparticle tracking analysis and flow cytometry. Functional effects were assessed through PBMC co-culture assays and murine transplantation experiments. Both NT2 and control (C2) cells were injected into C57/Bl mice, resulting in teratoma formation within 21 days. Teratomas were analyzed histologically and by immunostaining for CD4/8 and CD86 markers.
Circulating EVs were profiled using MACSPlex, while immune cell populations were quantified via flow cytometry and automated analysis.
Results:
NT2-derived EVs expressed canonical markers (AnnexinV, CD81) and carried multiple immunomodulatory proteins including SerpinB9, PD-L1, CD47, and CD200, which were reduced or absent in controls. In vitro, both NT2 cells and their EVs significantly decreased activated CD4+ and CD8+ T cell numbers. In vivo, mice with NT2-derived teratomas showed reduced circulating CD4+ and CD8+ T cells and monocytes, indicating systemic immunosuppression. Additionally, increased levels of platelet- and endothelial-derived EVs and shifts in CD4+/CD8+ EV ratios were observed.
Conclusion:
NT2-derived vesicles exert strong immunosuppressive effects, supporting their potential as cell-free therapeutic tools in transplantation and autoimmune diseases.
Funding:
TKP2021-EGA-23; RRF-2.3.121-2022-00003; 2019-2.1.7-ERA-NET-2021-00015; EU Horizon 2020 (No. 739593); NKFIH 150767.
Semmelweis University
Hargita Hegyesi
I do not give consent to the publication of my abstract on the website of the congress.
before finishing undergraduate studies (TDK, MD-PhD)
Szabad
elfogadva
szóbeli
jóváhagyta
9130
14:45
14:55