TY  - JOUR
A1  - Hinderer, Svenja
A1  - Shen, Nian
A1  - Ringuette, Léa-Jeanne
A1  - Hansmann, Jan
A1  - Reinhardt, Dieter P
A1  - Brucker, Sara Y
A1  - Davis, Elaine C
A1  - Schenke-Layland, Katja
T1  - In vitro elastogenesis: instructing human vascular smooth muscle cells to generate an elastic fiber-containing extracellular matrix scaffold
JF  - Biomedical Materials
N2  - Elastic fibers are essential for the proper function of organs including cardiovascular tissues such as heart valves and blood vessels. Although (tropo)elastin production in a tissue-engineered construct has previously been described, the assembly to functional elastic fibers in vitro using human cells has been highly challenging. In the present study, we seeded primary isolated human vascular smooth muscle cells (VSMCs) onto 3D electrospun scaffolds and exposed them to defined laminar shear stress using a customized bioreactor system. Increased elastin expression followed by elastin deposition onto the electrospun scaffolds, as well as on newly formed fibers, was observed after six days. Most interestingly, we identified the successful deposition of elastogenesis-associated proteins, including fibrillin-1 and -2, fibulin-4 and -5, fibronectin, elastin microfibril interface located protein 1 (EMILIN-1) and lysyl oxidase (LOX) within our engineered constructs. Ultrastructural analyses revealed a developing extracellular matrix (ECM) similar to native human fetal tissue, which is composed of collagens, microfibrils and elastin. To conclude, the combination of a novel dynamic flow bioreactor and an electrospun hybrid polymer scaffold allowed the production and assembly of an elastic fiber-containing ECM.
KW  - elastin
KW  - elastic fibers
KW  - electrospinning
KW  - tissue engineering
KW  - regenerative medicine
KW  - heart valve
KW  - cardiovascular
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-254074
VL  - 10
IS  - 3
ER  - 
TY  - JOUR
A1  - Alepee, Natalie
A1  - Bahinski, Anthony
A1  - Daneshian, Mardas
A1  - De Weyer, Bart
A1  - Fritsche, Ellen
A1  - Goldberg, Alan
A1  - Hansmann, Jan
A1  - Hartung, Thomas
A1  - Haycock, John
A1  - Hogberg, Helena T.
A1  - Hoelting, Lisa
A1  - Kelm, Jens M.
A1  - Kadereit, Suzanne
A1  - McVey, Emily
A1  - Landsiedel, Robert
A1  - Leist, Marcel
A1  - Lübberstedt, Marc
A1  - Noor, Fozia
A1  - Pellevoisin, Christian
A1  - Petersohn, Dirk
A1  - Pfannenbecker, Uwe
A1  - Reisinger, Kerstin
A1  - Ramirez, Tzutzuy
A1  - Rothen-Rutishauser, Barbara
A1  - Schäfer-Korting, Monika
A1  - Zeilinger, Katrin
A1  - Zurich, Marie-Gabriele
T1  - State-of-the-Art of 3D Cultures (Organs-on-a-Chip) in Safety Testing and Pathophysiology
JF  - ALTEX - Alternatives to Animal Experimentation
N2  - Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This review summarizes the state of the art concerning commonalities of the different models. For instance, the theory of mass transport/metabolite exchange in 3D systems and the special analytical requirements for test endpoints in organotypic cultures are discussed in detail. In the next part, 3D model systems for selected organs liver, lung, skin, brain are presented and characterized in dedicated chapters. Also, 3D approaches to the modeling of tumors are presented and discussed. All chapters give a historical background, illustrate the large variety of approaches, and highlight up- and downsides as well as specific requirements. Moreover, they refer to the application in disease modeling, drug discovery and safety assessment. Finally, consensus recommendations indicate a roadmap for the successful implementation of 3D models in routine screening. It is expected that the use of such models will accelerate progress by reducing error rates and wrong predictions from compound testing.
KW  - 3D models
KW  - organotypic
KW  - organ-on-a-chip
KW  - multicellular tumor spheroids
KW  - primary human hepatocytes
KW  - embryonic stem cell
KW  - reconstructed human epidermis
KW  - in-vitro models
KW  - full thickness skin
KW  - necrosis-factor-alpha
KW  - metabolic flux analysis
KW  - long-term
KW  - human liver cells
Y1  - 2014
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-117826
VL  - 31
IS  - 4
ER  -