PhD Scientific Days 2026

Poster Session 2.Q - Cardiovascular Medicine and Research

Investigating Cell-Matrix Interactions in Lamin A/C-related Dilated Cardiomyopathy via Stem Cell-derived Tissue Engineering Models

Name of the presenter

Maczelka, Hédi Nóra

Institute/workplace of the presenter

Heart and Vascular Center, Semmelweis University, Budapest, Hungary

Authors

Hédi Nóra Maczelka¹, Barbara Orsolits¹, Lilla Jázmin Bakos¹, Ildikó Mária Ványi¹, Luca Anna Joó-Bors¹, Márton Sághi², Béla Merkely¹, Ágota Apáti³, Gábor Földes¹
1: Heart and Vascular Center, Semmelweis University, Budapest, Hungary
2: Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
3: Institute of Molecular Life Sciences, HUN-REN Research Centre for Natural Sciences, Budapest, Hungary

Text of the abstract

Introduction
LMNA-related dilated cardiomyopathy (DCM) is a severe cardiac disorder marked by poor prognosis and high mortality. Endothelial dysfunction induced by LMNA mutations may play a key role in DCM pathogenesis, though the specific endothelial phenotype in this cardiovascular disease remains unclear. However, the specific endothelial phenotype associated with LMNA-related DCM is poorly understood.
Aims
In this study, a human induced pluripotent stem cell (hiPSC)-based tissue-engineered model have been used in order to investigate how LMNA mutations influence endothelial cell (EC) behavior and extracellular matrix (ECM) interactions in DCM.
Methods
Heart tissue samples were collected from healthy donors (n=7) and DCM patients with confirmed LMNA mutations (n=10) from the Semmelweis University Heart and Vascular Centre Transplantation Biobank. Histological and immunohistochemical quantification were used to assess tissue remodeling, while ECM composition was characterized via LC-MS/MS proteomics. Endothelial differentiation was performed on healthy (n=3) and LMNA-mutant (n=3) hiPSC lines, which were subsequently phenotypically and functionally characterised by immunohistochemistry, scratch and tube formation assay. After performing decellularisation on both healthy and diseased cardiac tissues, and the generated cell-free matrices were reseeded with the generated healthy and LMNA-mutant hiPSC-derived ECs and were assessed by immunohistochemistry.
Results
The DCM tissues showed significant cardiomyocyte hypertrophy, pericellular fibrosis, and capillary rarefaction. Immunohistochemistry revealed elevated interstitial levels of 9 and elevated perivascular levels of 8 proteins in DCM tissue samples. Proteomic analysis identified 192 ECM proteins, with 13 significantly overexpressed in DCM tissues (p<0.05). Comparing hiPSC-derived ECs, the healthy and LMNA-mutant cells showed difference in angiogenetic potential and differentiation capacity, but not in morphology and motility. Recellularised matrices supported endothelial phenotype maintenance, viability, long-term proliferation, and functional maturation.
Conclusions
This hiPSC-based model provides detailed insights into cell-ECM interactions and potential molecular mechanisms underlying endothelial dysfunction in LMNA-associated DCM.
Funding
Funded by RRF-2.3.1-21-2022-00003, TKP2021-EGA-23, and OTKA K146125.