PhD Scientific Days 2025

Poster Session I. - A: Molecular Medicine

The Effect of Extracellular Vesicles from Mesenchymal Cells of Peritoneal Dialysate on the Mechanism of Fibrosis

Name of the presenter

Bokrossy Péter

Institute/workplace of the presenter

Budapest, Bókay János u. 53-54, 1083

Authors

Péter Bokrossy¹, Beáta Szebeni², Apor Veres-Székely², Domonkos Pap², Zoltán Varga³, Judith Mihály³, Éva Pállinger⁴, Attila J. Szabó², Ádám Vannay²

1: Budapest, Bókay János u. 53-54, 1083
2: Pediatric Center, MTA Center of Excellence, Semmelweis University, Budapest, Hungary;HUN-REN–SU Pediatrics and Nephrology Research Group, Budapest, Hungary
3: TTK Biological Nanochemistry Research Group, Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Budapest, Hungary;
4: Department of Genetics, Cell- and Immunobiology, Semmelweis University, Budapest, Hungary;

Text of the abstract

Introduction: The literature is abundant in the topic of benefits of cell therapy in different experimental fibrosis models. Using extracellular vesicles (EVs) as an alternative to cell therapy promises benefits like lower imunnogenicity, a possible crossing of the blood-brain barrier, and not inducing acute immune rejection.
Aims: We investigated the effect of EVs originated from mesenchymal cells (MCs) of peritoneal dialysate (PDE) on the activation of fibroblasts and human peripheral blood mononuclear cells (PBMCs).
Methods: MCs were isolated, characterised and cultured from PDE. From the cultures supernatant EVs were isolated by tangential flow filtration and size exclusion chromatography. After the isolation EVs were characterized based on their particle number, size distribution, morphology, surface markers, and the composition of cargo proteins. Their effect on fibroblast activation was tested by in vitro experiments on primary peritoneal fibroblasts (pFBs). The effect of EVs on the pFBs were examined by using functional assays such as MTT proliferation assay, Sirius Red assay and Transient Agarose Spot assay. The EVs effect on PBMCs were examined by RT-PCR. The effect of EVs on peritoneal fibrosis was investigated in a chlorhexidine digluconate-induced mouse model.
Results: The mesenchymal cells isolated from PDE displayed positive expressions of CK-18, α-SMA, CD73, CD105, and CD90. The isolated EVs exhibited stem cell and CK18 positivity, implying that their original source cells were MCs that had undergone mesothelial mesenchymal transition. The EVs successfully internalised by pFBs and reduced their induced proliferation, collagen accumulation and migration as shown by various functionals assays. EVs increased PBMCs IL-10, IL-6 and MCP-1 expression. EVs also prevented peritoneal fibrosis in vivo.
Conclusion: Due to the potential antifibrotic properties exhibited by these extracellular vesicles (EVs), they could hold therapeutic promise. Nevertheless, further in vivo testing is required to substantiate this hypothesis.
Funding: NKFIH K-142728, K-131594; 2020-1-1-2-PIACI-KFI_2020-00021, TKP2021-EGA-24, TKP2021-EGA-31, RRF-2.3.1-21- 2022-00003; HUN-REN, ELKH-POC-2022-024, EKÖP-2024-53; EKÖP-2024-160; EKÖP-2024-162, ÚNKP-23-5-SE-15, János Bolyai Research Scholarship.
Bokrossy.p@gmail.com
Semmelweis University
Supervisor: Ádám Vannay