TY  - JOUR
A1  - Doryab, Ali
A1  - Taskin, Mehmet Berat
A1  - Stahlhut, Philipp
A1  - Schröppel, Andreas
A1  - Orak, Sezer
A1  - Voss, Carola
A1  - Ahluwalia, Arti
A1  - Rehberg, Markus
A1  - Hilgendorff, Anne
A1  - Stöger, Tobias
A1  - Groll, Jürgen
A1  - Schmid, Otmar
T1  - A Bioinspired in vitro Lung Model to Study Particokinetics of Nano-/Microparticles Under Cyclic Stretch and Air-Liquid Interface Conditions
JF  - Frontiers in Bioengineering and Biotechnology
N2  - Evolution has endowed the lung with exceptional design providing a large surface area for gas exchange area (ca. 100 m\(^{2}\)) in a relatively small tissue volume (ca. 6 L). This is possible due to a complex tissue architecture that has resulted in one of the most challenging organs to be recreated in the lab. The need for realistic and robust in vitro lung models becomes even more evident as causal therapies, especially for chronic respiratory diseases, are lacking. Here, we describe the Cyclic In VItro Cell-stretch (CIVIC) “breathing” lung bioreactor for pulmonary epithelial cells at the air-liquid interface (ALI) experiencing cyclic stretch while monitoring stretch-related parameters (amplitude, frequency, and membrane elastic modulus) under real-time conditions. The previously described biomimetic copolymeric BETA membrane (5 μm thick, bioactive, porous, and elastic) was attempted to be improved for even more biomimetic permeability, elasticity (elastic modulus and stretchability), and bioactivity by changing its chemical composition. This biphasic membrane supports both the initial formation of a tight monolayer of pulmonary epithelial cells (A549 and 16HBE14o\(^{-}\)) under submerged conditions and the subsequent cell-stretch experiments at the ALI without preconditioning of the membrane. The newly manufactured versions of the BETA membrane did not improve the characteristics of the previously determined optimum BETA membrane (9.35% PCL and 6.34% gelatin [w/v solvent]). Hence, the optimum BETA membrane was used to investigate quantitatively the role of physiologic cyclic mechanical stretch (10% linear stretch; 0.33 Hz: light exercise conditions) on size-dependent cellular uptake and transepithelial transport of nanoparticles (100 nm) and microparticles (1,000 nm) for alveolar epithelial cells (A549) under ALI conditions. Our results show that physiologic stretch enhances cellular uptake of 100 nm nanoparticles across the epithelial cell barrier, but the barrier becomes permeable for both nano- and micron-sized particles (100 and 1,000 nm). This suggests that currently used static in vitro assays may underestimate cellular uptake and transbarrier transport of nanoparticles in the lung.
KW  - lung cell model
KW  - cyclic stretch
KW  - ALI culture
KW  - bioinspired membrane
KW  - particle study
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-223830
SN  - 2296-4185
VL  - 9
ER  - 
TY  - JOUR
A1  - Chillo, Omary
A1  - Kleinert, Eike Christian
A1  - Lautz, Thomas
A1  - Lasch, Manuel
A1  - Pagel, Judith-Irina
A1  - Heun, Yvonn
A1  - Troidl, Kerstin
A1  - Fischer, Silvia
A1  - Caballero-Martinez, Amelia
A1  - Mauer, Annika
A1  - Kurz, Angela R. M.
A1  - Assmann, Gerald
A1  - Rehberg, Markus
A1  - Kanse, Sandip M.
A1  - Nieswandt, Bernhard
A1  - Walzog, Barbara
A1  - Reichel, Christoph A.
A1  - Mannell, Hanna
A1  - Preissner, Klaus T.
A1  - Deindl, Elisabeth
T1  - Perivascular Mast Cells Govern Shear Stress-Induced Arteriogenesis by Orchestrating Leukocyte Function
JF  - Cell Reports
N2  - The body has the capacity to compensate for an occluded artery by creating a natural bypass upon increased fluid shear stress. How this mechanical force is translated into collateral artery growth (arteriogenesis) is unresolved. We show that extravasation of neutrophils mediated by the platelet receptor GPIbα and uPA results in Nox2-derived reactive oxygen radicals, which activate perivascular mast cells. These c-kit+/CXCR-4+ cells stimulate arteriogenesis by recruiting additional neutrophils as well as growth-promoting monocytes and T cells. Additionally, mast cells may directly contribute to vascular remodeling and vascular cell proliferation through increased MMP activity and by supplying growth-promoting factors. Boosting mast cell recruitment and activation effectively promotes arteriogenesis, thereby protecting tissue from severe ischemic damage. We thus find that perivascular mast cells are central regulators of shear stress-induced arteriogenesis by orchestrating leukocyte function and growth factor/cytokine release, thus providing a therapeutic target for treatment of vascular occlusive diseases.
KW  - Mast cells
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-164800
VL  - 16
IS  - 8
ER  -