@phdthesis{Sun2022,
  author    = {Sun, Xianlei},
  title     = {Elasticity of fiber meshes derived from multiblock copolymers influences cell behaviors},
  doi       = {10.25932/publishup-53528},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-535285},
  school      = {Universit{\"a}t Potsdam},
  pages     = {96},
  year      = {2022},
  abstract  = {Objective: The behaviors of endothelial cells or mesenchymal stem cells are remarkably influenced by the mechanical properties of their surrounding microenvironments. Here, electrospun fiber meshes containing various mechanical characteristics were developed from polyetheresterurethane (PEEU) copolymers. The goal of this study was to explore how fiber mesh stiffness affected endothelial cell shape, growth, migration, and angiogenic potential of endothelial cells. Furthermore, the effects of the E-modulus of fiber meshes on human adipose-derived stem cells (hADSCs) osteogenic potential was investigated. Methods: Polyesteretherurethane (PEEU) polymers with various poly(p-dioxanone) (PPDO) to poly (ε-caprolactone) (PCL) weight percentages (40 wt.\%, 50 wt.\%, 60 wt.\%, and 70 wt.\%) were synthesized, termed PEEU40, PEEU50, PEEU60, and PEEU70, accordingly. The electrospinning method was used for the preparation of PEEU fiber meshes. The effects of PEEU fiber meshes with varying elasticities on the human umbilical vein endothelial cells (HUVECs) shape, growth, migration and angiogenic potential were characterized. To determine how the E-modulus of fiber meshes affects the osteogenic potential of hADSCs, the cellular and nuclear morphologies and osteogenic differentiation abilities were evaluated. Results: With the increasing stiffness of PEEU fiber meshes, the aspect ratios of HUVECs cultivated on PEEU materials increased. HUVECs cultivated on high stiffness fiber meshes (4.5 ± 0.8 MPa) displayed a considerably greater proliferation rate and migratory velocity, in addition demonstrating increased tube formation capability, compared with those of the cells cultivated on lower stiffness fiber meshes (2.6 ± 0.8 MPa). Furthermore, in comparison to those cultivated on lower stiffness fiber meshes, hADSCs adhered to the highest stiffness fiber meshes PEEU70 had an elongated shape. The hADSCs grown on the softer PEEU40 fiber meshes showed a reduced nuclear aspect ratio (width to height) than those cultivated on the stiffer fiber meshes. Culturing hADSCs on stiffer fibers improved their osteogenic differentiation potential. Compared with cells cultured on PEEU40, osteocalcin expression and alkaline phosphatase (ALP) activity increased by 73 ± 10\% and 43 ± 16\%, respectively, in cells cultured on PEEU70. Conclusion: The mechanical characteristics of the substrate are crucial in the modulation of cell behaviors. These findings indicate that adjusting the elasticity of fiber meshes might be a useful method for controlling the blood vessels development and regeneration. Furthermore, the mechanical characteristics of PEEU fiber meshes might be modified to control the osteogenic potential of hADSCs.},
  language  = {en}
}
@article{RoedelAbdelilahSeyfried2021,
  author    = {R{\"o}del, Claudia Jasmin and Abdelilah-Seyfried, Salim},
  title     = {A zebrafish toolbox for biomechanical signaling in cardiovascular development and disease},
  series = {Current opinion in hematology},
  volume    = {28},
  journal   = {Current opinion in hematology},
  number    = {3},
  publisher = {Lippincott Williams \& Wilkins},
  address   = {Philadelphia},
  issn      = {1065-6251},
  doi       = {10.1097/MOH.0000000000000648},
  pages     = {198 -- 207},
  year      = {2021},
  abstract  = {Purpose of review The zebrafish embryo has emerged as a powerful model organism to investigate the mechanisms by which biophysical forces regulate vascular and cardiac cell biology during development and disease. A versatile arsenal of methods and tools is available to manipulate and analyze biomechanical signaling. This review aims to provide an overview of the experimental strategies and tools that have been utilized to study biomechanical signaling in cardiovascular developmental processes and different vascular disease models in the zebrafish embryo. Within the scope of this review, we focus on work published during the last two years. Recent findings Genetic and pharmacological tools for the manipulation of cardiac function allow alterations of hemodynamic flow patterns in the zebrafish embryo and various types of transgenic lines are available to report endothelial cell responses to biophysical forces. These tools have not only revealed the impact of biophysical forces on cardiovascular development but also helped to establish more accurate models for cardiovascular diseases including cerebral cavernous malformations, hereditary hemorrhagic telangiectasias, arteriovenous malformations, and lymphangiopathies. Summary The zebrafish embryo is a valuable vertebrate model in which in-vivo manipulations of biophysical forces due to cardiac contractility and blood flow can be performed. These analyses give important insights into biomechanical signaling pathways that control endothelial and endocardial cell behaviors. The technical advances using this vertebrate model will advance our understanding of the impact of biophysical forces in cardiovascular pathologies.},
  language  = {en}
}
@article{OttenKnoxBouldayetal.2018,
  author    = {Otten, Cecile and Knox, Jessica and Boulday, Gwenola and Eymery, Mathias and Haniszewski, Marta and Neuenschwander, Martin and Radetzki, Silke and Vogt, Ingo and Haehn, Kristina and De Luca, Coralie and Cardoso, Cecile and Hamad, Sabri and Igual Gil, Carla and Roy, Peter and Albiges-Rizo, Corinne and Faurobert, Eva and von Kries, Jens P. and Campillos, Monica and Tournier-Lasserve, Elisabeth and Derry, William Brent and Abdelilah-Seyfried, Salim},
  title     = {Systematic pharmacological screens uncover novel pathways involved in cerebral cavernous malformations},
  series = {EMBO molecular medicine},
  volume    = {10},
  journal   = {EMBO molecular medicine},
  number    = {10},
  publisher = {Wiley},
  address   = {Hoboken},
  issn      = {1757-4676},
  doi       = {10.15252/emmm.201809155},
  pages     = {17},
  year      = {2018},
  abstract  = {Cerebral cavernous malformations (CCMs) are vascular lesions in the central nervous system causing strokes and seizures which currently can only be treated through neurosurgery. The disease arises through changes in the regulatory networks of endothelial cells that must be comprehensively understood to develop alternative, non-invasive pharmacological therapies. Here, we present the results of several unbiased small-molecule suppression screens in which we applied a total of 5,268 unique substances to CCM mutant worm, zebrafish, mouse, or human endothelial cells. We used a systems biology-based target prediction tool to integrate the results with the whole-transcriptome profile of zebrafish CCM2 mutants, revealing signaling pathways relevant to the disease and potential targets for small-molecule-based therapies. We found indirubin-3-monoxime to alleviate the lesion burden in murine preclinical models of CCM2 and CCM3 and suppress the loss-of-CCM phenotypes in human endothelial cells. Our multi-organism-based approach reveals new components of the CCM regulatory network and foreshadows novel small-molecule-based therapeutic applications for suppressing this devastating disease in patients.},
  language  = {en}
}
@misc{OlmerEngelsUsmanetal.2018,
  author    = {Olmer, Ruth and Engels, Lena and Usman, Abdulai and Menke, Sandra and Malik, Muhammad Nasir Hayat and Pessler, Frank and G{\"o}hring, Gudrun and Bornhorst, Dorothee and Bolten, Svenja and Abdelilah-Seyfried, Salim and Scheper, Thomas and Kempf, Henning and Zweigerdt, Robert and Martin, Ulrich},
  title     = {Differentiation of Human Pluripotent Stem Cells into Functional Endothelial Cells in Scalable Suspension Culture},
  series = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  journal   = {Postprints der Universit{\"a}t Potsdam : Mathematisch-Naturwissenschaftliche Reihe},
  number    = {5},
  issn      = {1866-8372},
  doi       = {10.25932/publishup-42709},
  url       = {http://nbn-resolving.de/urn:nbn:de:kobv:517-opus4-427095},
  pages     = {18},
  year      = {2018},
  abstract  = {Endothelial cells (ECs) are involved in a variety of cellular responses. As multifunctional components of vascular structures, endothelial (progenitor) cells have been utilized in cellular therapies and are required as an important cellular component of engineered tissue constructs and in vitro disease models. Although primary ECs from different sources are readily isolated and expanded, cell quantity and quality in terms of functionality and karyotype stability is limited. ECs derived from human induced pluripotent stem cells (hiPSCs) represent an alternative and potentially superior cell source, but traditional culture approaches and 2D differentiation protocols hardly allow for production of large cell numbers. Aiming at the production of ECs, we have developed a robust approach for efficient endothelial differentiation of hiPSCs in scalable suspension culture. The established protocol results in relevant numbers of ECs for regenerative approaches and industrial applications that show in vitro proliferation capacity and a high degree of chromosomal stability.},
  language  = {en}
}
@article{OlmerEngelsUsmanetal.2018,
  author    = {Olmer, Ruth and Engels, Lena and Usman, Abdulai and Menke, Sandra and Malik, Muhammad Nasir Hayat and Pessler, Frank and Goehring, Gudrun and Bornhorst, Dorothee and Bolten, Svenja and Abdelilah-Seyfried, Salim and Scheper, Thomas and Kempf, Henning and Zweigerdt, Robert and Martin, Ulrich},
  title     = {Differentiation of Human Pluripotent Stem Cells into Functional Endothelial Cells in Scalable Suspension Culture},
  series = {Stem Cell Reports},
  volume    = {10},
  journal   = {Stem Cell Reports},
  number    = {5},
  publisher = {Springer},
  address   = {New York},
  issn      = {2213-6711},
  doi       = {10.1016/j.stemcr.2018.03.017},
  pages     = {16},
  year      = {2018},
  abstract  = {Endothelial cells (ECs) are involved in a variety of cellular responses. As multifunctional components of vascular structures, endothelial (progenitor) cells have been utilized in cellular therapies and are required as an important cellular component of engineered tissue constructs and in vitro disease models. Although primary ECs from different sources are readily isolated and expanded, cell quantity and quality in terms of functionality and karyotype stability is limited. ECs derived from human induced pluripotent stem cells (hiPSCs) represent an alternative and potentially superior cell source, but traditional culture approaches and 2D differentiation protocols hardly allow for production of large cell numbers. Aiming at the production of ECs, we have developed a robust approach for efficient endothelial differentiation of hiPSCs in scalable suspension culture. The established protocol results in relevant numbers of ECs for regenerative approaches and industrial applications that show in vitro proliferation capacity and a high degree of chromosomal stability.},
  language  = {en}
}