TY  - JOUR
AU  - Gögele, Clemens
AU  - Hoffmann, Christina
AU  - Konrad, Jens
AU  - Merkel, Rudolf
AU  - Schwarz, Silke
AU  - Tohidnezhad, Mersedeh
AU  - Hoffmann, Bernd
AU  - Schulze-Tanzil, Gundula Gesine
TI  - Cyclically stretched ACL fibroblasts emigrating from spheroids adapt their cytoskeleton and ligament-related expression profile
JO  - Cell & tissue research
VL  - 384
IS  - 3
SN  - 1432-0878
CY  - Heidelberg
PB  - Springer
M1  - FZJ-2021-04073
SP  - 675 - 690
PY  - 2021
AB  - Mechanical stress of ligaments varies; hence, ligament fibroblasts must adapt their expression profile to novel mechanomilieus to ensure tissue resilience. Activation of the mechanoreceptors leads to a specific signal transduction, the so-called mechanotransduction. However, with regard to their natural three-dimensional (3D) microenvironment cell reaction to mechanical stimuli during emigrating from a 3D spheroid culture is still unclear. This study aims to provide a deeper understanding of the reaction profile of anterior cruciate ligament (ACL)-derived fibroblasts exposed to cyclic uniaxial strain in two-dimensional (2D) monolayer culture and during emigration from 3D spheroids with respect to cell survival, cell and cytoskeletal orientation, distribution, and expression profile. Monolayers and spheroids were cultured in crosslinked polydimethyl siloxane (PDMS) elastomeric chambers and uniaxially stretched (14% at 0.3 Hz) for 48 h. Cell vitality, their distribution, nuclear shape, stress fiber orientation, focal adhesions, proliferation, expression of ECM components such as sulfated glycosaminoglycans, collagen type I, decorin, tenascin C and cell–cell communication-related gap junctional connexin (CXN) 43, tendon-related markers Mohawk and tenomodulin (myodulin) were analyzed. In contrast to unstretched cells, stretched fibroblasts showed elongation of stress fibers, cell and cytoskeletal alignment perpendicular to strain direction, less rounded cell nuclei, increased numbers of focal adhesions, proliferation, amplified CXN43, and main ECM component expression in both cultures. The applied cyclic stretch protocol evoked an anabolic response and enhanced tendon-related marker expression in ACL-derived fibroblasts emigrating from 3D spheroids and seems also promising to support in future tissue formation in ACL scaffolds seeded in vitro with spheroids.
LB  - PUB:(DE-HGF)16
C6  - pmid:33835257
UR  - <Go to ISI:>//WOS:000638485300001
DO  - DOI:10.1007/s00441-021-03416-9
UR  - https://juser.fz-juelich.de/record/902164
ER  -