Three-dimensional (3D) cellular systems
Retinal Organoids
We focus on modeling the retinal neurovascular unit (rNVU), which is the functional connection between retinal nerves and blood vessels. Because dysfunction in this unit leads to vision loss, the study aims to recreate the Outer Blood-Retinal Barrier—the critical gatekeeper between the neural retina and the choroid—using advanced cellular engineering. Our plan is to generate an innovative humanized in vitro retinal model (retina-on-a chip,ROC). Specifically, we develop a three-dimensional tissue construct consisting of RPE cells, neural cells(ROs) and vessels, all derived from hPSCs in the relevant anatomical layout within a microfluidic system, in order to develop the main blood-retinal-barrier (BRB) and achieve the dynamic interaction of the different cell types.
Apostolidi A, Stergiopoulos G, Bellou S, Markou M, Fotsis T, Murphy C, Bagli E. Advances in Modeling the Inner Blood-Retinal Barrier: From Static Tissue Cell Cultures to Microphysiological Systems. Pharmaceuticals (Basel). 2025 Sep 13;18(9):1374. doi: 10.3390/ph18091374. PMID: 41011242; PMCID: PMC12472624.
Vascular organoids
Transplantation of mono-cells in vivo is usually characterized by low survival rate. Moreover, the lack of Smooth Muscle Cell (SMC) culture homogeneity at a specific differentiation stage, the SMC phenotypic plasticity as well as the fact that SMC phenotype and function are tightly regulated by their surrounding microenvironment and by their organization within the tissue, all indicate a high risk of SMCs to acquire an unfavorable (inflammatory) phenotype, when implanted as monocells in a hostile environment. These obstacles could be overcome by the generation of 3D cell structures (small-scale vascular organoids) containing both ECs and SMCs subtypes, which unlike traditional 2D monolayer cultures, would provide enhanced cell–cell interactions that closely mimic the natural/physiological tissue microenvironment with beneficial effects on cell survival, phenotypic stability and function, when transplanted in vivo
Generation and Immunophenotypic characterization of vascular organoids.
Markou M, Kouroupis D, Badounas F, Katsouras A, Kyrkou A, Fotsis T, Murphy C, Bagli E. Tissue Engineering Using Vascular Organoids From Human Pluripotent Stem Cell Derived Mural Cell Phenotypes. Front Bioeng Biotechnol. 2020 Apr 17;8:278. doi: 10.3389/fbioe.2020.00278. PMID: 32363181; PMCID: PMC7182037
