Browsing by Subject "endothelial cell"

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  • Riederer, Monika; Ojala, Pauli J.; Hrzenjak, Andelko; Tritscher, Michaela; Hermansson, Martin; Watzer, Bernhard; Schweer, Horst; Desoye, Gernot; Heinemann, Akos; Frank, Sasa (2010)
  • Rautiainen, Swarna (Helsingin yliopisto, 2020)
    Endothelial dysfunction is a common characteristic of several diseases including diabetes mellitus, coronary heart disease and stroke. Healthy endothelium ensures vascular homeostasis, regulation of blood flow and the exchange of oxygen and nutrients, as well as immune cell filtration to the surrounding tissues. In many cases, endothelial dysfunction results in ischemia in the surrounding tissues impairing cellular regeneration mechanisms, which can lead to tissue necrosis in the worst case. Therapeutic angiogenesis via stem cell transplantation aims to restore tissue blood flow and thus aid in tissue regeneration and restoration of a functioning tissue. Adipose derived stem/stromal cells (ASC) are a stem cell population with a multilineage differentiation ability. They have been shown to differentiate towards adipogenic, osteogenic, chondrogenic, myogenic and neurogenic lineages among others. Their easy obtainability from liposuction material and abundance in the adipose tissue makes them an especially practical and favorable cell option for stem cell research. In angiogenesis research, ASCs are commonly used in a co-culture with an endothelial cell (EC) type such as human umbilical vein endothelial cell. ASCs secrete extracellular vesicles (EV) that are small membrane bound vesicles with a diameter ranging from 40-1000 nm, and which have the ability to alter the behavior of target cells through their cargo. EV cargo consists of microRNAs, messenger-RNAs and proteins, and the EV cargo of ASCs has been shown to have proangiogenic effects. The aim of this work was to review what is currently known about ASC ability to promote angiogenesis through paracrine secretion and differentiation into endothelial cells or pericytes, interactions between ASCs and endothelial cells in the angiogenesis promoting process and the role of ASC extracellular vesicles in promoting angiogenesis. The methods for this work were database research of related articles using scientific databases and search engines, article categorization and reading, and finally manuscript production. It can be concluded from the current literature that a co-culture environment of ASCs and an endothelial cell type supports the formation of tube-like structures in vitro. Additional insulin like growth factor 1 in culture medium enhances the expression of angiogenesis-related growth factors in both cell types via PI3K/AKT signaling pathway. Further, the activation of platelet derived growth factor receptor β supports ASC ability to promote vascular network formation. On the contrary, the presence of ASC secreted activin A results in the inhibition of vascular network formation. ASCs can differentiate into endothelial cells particularly in three-dimensional culture conditions. In addition, fibroblast growth factor 2 and the activation of the AKT-pathway are crucial for endothelial differentiation. In addition, ASCs have the ability to differentiate into pericytes and assume a stabilizing role on the outside of the microvessels. Concerning ASC derived EVs and their cargo, miR-31, miR-125a and miR-126 have proangiogenic effects in vitro and in vivo. Proangiogenic miRNAs in ASC EV cargo are miR-181b-5p and the let7-family, out of which miR-181b-5p upregulates vascular endothelial growth factor and hypoxia-inducible factor 1α and let7-family influences tube formation ability of ECs. In vivo, ASC derived EVs support fat grafting, enhance wound healing both in healthy and diabetic environment, and provide cardioprotection. Therefore, ASC EVs show potential for therapeutic angiogenesis but currently there is a lack of clinical trials in EV research.
  • Talman, Virpi; Kivelä, Milla Riikka (2018)
    The heart is a complex organ consisting of various cell types, each of which plays an important role in both physiological and pathophysiological conditions. The cells communicate with each other through direct cell-cell interactions and paracrine signaling, and both homotypic and heterotypic cell interactions contribute to the organized structure and proper function of the heart. Cardiomyocytes (CMs) and endothelial cells (ECs) are two of the most abundant cardiac cell types and they also play central roles in both cardiac remodeling and regeneration. The postnatal cell cycle withdrawal of CMs, which takes place within days or weeks after birth, represents the major barrier for regeneration in adult mammalian hearts, as adult CMs exhibit a very low proliferative capacity. Recent evidence highlights the importance of ECs not only as the most abundant cell type in the heart but also as key players in post-infarction remodeling and regeneration. In this MiniReview, we focus on blood vascular ECs and CMs and their roles and interactions in cardiac physiology and pathologies, with a special emphasis on cardiac regeneration. We summarize the known mediators of the bidirectional CM-EC interactions and discuss the related recent advances in the development of therapies aiming to promote heart repair and regeneration targeting these two cell types.
  • Taskinen, Juuso (Helsingin yliopisto, 2019)
    Human umbilical vein endothelial cells are responsible for maintaining and forming new vessels from existing ones, in a biological process called sprouting angiogenesis. Sprouting angiogenesis is a crucial mechanism for the resolution of hypoxia and normal development of tissues. It also plays a key role in internal plague hemorrhages, which can lead to embolisms and other cardiovascular complications. Angiogenesis is also crucial for cancer development. Sprouting angiogenesis is initiated by hypoxic tissue excreted vascular endothelial growth factor gradient, which induces normal endothelial cells into either a proliferative stalk cell or a signal sensing tip cell phenotype. Both of these cell types depend on the rapid flow of lipids to their plasma membrane, either to form plasma membrane protrusions in tip cells or as new plasma membrane material in dividing stalk cells. This flow is envisioned to involve both vesicle-mediated and non-vesicular mechanisms. A major non-vesicular route of lipid transfer occurs at membrane contact sites via lipid transport proteins. Furthermore, lipids can be transported to the plasma membrane by the direct fusion of vesicles or endosomes with the plasma membrane This thesis set out to explore the role of two membrane contact site proteins, oxysterol-binding protein- related protein 2 and protrudin, in angiogenesis and lipid transfer. Their role was examined by RNA-sequencing transient knock-down samples of these proteins in HUVECs. The RNA-sequencing data was examined by differential expression, gene ontology overrepresentation and gene set enrichment analyses. Gene expression analysis provided almost 10 000 significantly changed transcripts (adjusted p-values < 0.05), in each silenced cell type. The distribution of differentially expressed genes in oxysterol-binding protein- related protein 2 silenced cells, is skewed toward negative fold changes, whereas the distribution of differentially expressed genes in protrudin silenced samples is normally distributed. The results also show significant changes in gene ontologies related to proliferation, cell cycle, angiogenesis as well as hypoxia in both sample types. Gene set enrichment analysis showed upregulation in angiogenesis related pathways, such as the PI3K-Akt and MAPK pathways, in both samples. Significant downregulation was present in cell cycle related pathways and cholesterol biosynthesis pathway in both ORP2 and protrudin silenced samples.
  • Toropainen, Siiri (Helsingin yliopisto, 2020)
    Human induced pluripotent stem cells (hiPSC) can be propagated in a long-term culture and further differentiated into many cell types, including cardiomyocytes (CM) and endothelial cells (EC). Human induced pluripotent stem cell derived cardiomyocytes (hiPSC-CM) are promising tools in cardiac research, since they retain the original genotype of the individual donor and thus enable the use of patient- and disease specific cells. Crucial for the optimal use of hiPSC-CMs in experiments are methods for assessing cardiomyocyte phenotype. Contraction is a prominent feature for CMs, and it is essential that contraction can be quantified accurately. Reliable quantification is relevant when hiPSC-CMs are used for studying disease phenotypes, cardiac safety pharmacology, genotype-phenotype correlations, cardiac disease mechanisms and cardiac function over time. In this thesis project, contractile behavior of hiPSC-CMs was analyzed using video microscopy and online tool MUSCLEMOTION. Contraction parameters were obtained from hiPSC-CMs derived from patients with hypoplastic left heart syndrome (HLHS) and healthy controls on multiple timepoints during differentiation. In addition, contraction was analyzed in iPSC-CMs cocultured with induced pluripotent stem cell derived endothelial cells (iPSC-ECs), since it has been suggested that ECs can promote morphological and functional maturation of CMs in culture. Contraction duration (CD), time to peak (TTP), relaxation time (RT) and contraction amplitude (CA) was compared between different timepoints as well as between CMs cocultured with ECs and CMs cultured alone. Compared to control cell lines, HLHS patient hiPSC-CMs exhibited longer CD, TTP and RT as well as higher CA values. This difference was present in most of the timepoints, suggesting slower contractile kinetics in HLHS patient iPSC-CMs compared to control iPSC-CMs. Significant changes were also observed in contraction parameters when comparing hiPSC-CMs in coculture and monoculture. Contraction parameters of coculture iPSC-CMs changed in a relatively consistent manner over time, increasing or decreasing throughout the monitoring period whereas in hiPSC-CM monoculture there was more variation between timepoints. This project and results support the use of modern methods in detailed functional characterization of hiPSC-derived cells. In addition, it highlights the potential of coculture in disease modeling and the fact that hiPSC-CMs express variation in phenotypes. However, experiments should be repeated, and additional methods should be used in order to further validate the results and conclusions.
  • Kivelä, Milla Riikka; Bry, Maija; Robciuc, Marius R.; Räsänen, Markus; Taavitsainen, Miia; Silvola, Johanna M. U.; Saraste, Antti; Hulmi, Juha J.; Anisimov, Andrey; Mayranpaa, Mikko I.; Lindeman, Jan H.; Eklund, Lauri; Hellberg, Sanna; Hlushchuk, Ruslan; Zhuang, Zhen W.; Simons, Michael; Djonov, Valentin; Knuuti, Juhani; Mervaala, Eero; Alitalo, Kari (2014)