Advanced human cell-based models for venous malformations
Thesis event information
Date and time of the thesis defence
Place of the thesis defence
Leena Palotie auditorium (101A), the main building of the Kontinkangas Medical Campus, Aapistie 5A
Topic of the dissertation
Advanced human cell-based models for venous malformations
Doctoral candidate
Master of Science in Biomedical Engineering Mohammadhassan Ansarizadeh
Faculty and unit
University of Oulu Graduate School, Faculty of Biochemistry and Molecular Medicine, ECM and hypoxia
Subject of study
Biochemistry and molecular medicine
Opponent
Associate professor Jeroen Rouwkema, University of Twente
Custos
Professor Lauri Eklund , Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu, University of Oulu
Advanced human cell-based models for venous malformation
Venous malformations (VMs) are clusters of abnormal vein-like channels that develop due to improper formation of veins, often causing pain and swelling. Most VMs are caused by mutations in receptor tyrosine kinase TIE2, a gene expressed in endothelial cells in the blood vessel innermost cell layer. How TIE2 mutation leads to VMs is not fully understood, and current treatments are limited.
This thesis study aimed to create human cell-based lab models that mimic both normal and VM-affected blood vessels to better understand why VMs are formed and to test potential treatments. Different types of vessel-lining and supportive cells were used including genetically modified human umbilical vein, pluripotent stem cell, and VM biopsy-derived endothelial cells, that were co-cultured with the vessel supportive mesenchymal cells in co-culture models developed. The influence of flow was investigated in a microfluidic chip.
Results showed that TIE2-mutated cells formed abnormally large structures, mimicking VM patterns, which could be useful for drug testing. Mutated endothelial cells also interacted differently with the vessel supportive cells, changing their behavior and gene expression. The microfluidic model with simulated blood flow revealed that TIE2-mutated cells respond to flow differently from normal cells.
Since no cure exists for VMs, these human cell models offer a valuable tool for exploring disease mechanisms and finding potential treatments for VMs caused by TIE2 mutations.
This thesis study aimed to create human cell-based lab models that mimic both normal and VM-affected blood vessels to better understand why VMs are formed and to test potential treatments. Different types of vessel-lining and supportive cells were used including genetically modified human umbilical vein, pluripotent stem cell, and VM biopsy-derived endothelial cells, that were co-cultured with the vessel supportive mesenchymal cells in co-culture models developed. The influence of flow was investigated in a microfluidic chip.
Results showed that TIE2-mutated cells formed abnormally large structures, mimicking VM patterns, which could be useful for drug testing. Mutated endothelial cells also interacted differently with the vessel supportive cells, changing their behavior and gene expression. The microfluidic model with simulated blood flow revealed that TIE2-mutated cells respond to flow differently from normal cells.
Since no cure exists for VMs, these human cell models offer a valuable tool for exploring disease mechanisms and finding potential treatments for VMs caused by TIE2 mutations.
Last updated: 6.11.2024