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  • Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal Stem Cell-Extracellular Matrix Interactions.

Modeling of the Human Bone Environment: Mechanical Stimuli Guide Mesenchymal Stem Cell-Extracellular Matrix Interactions.

Materials (Basel, Switzerland) (2021-08-28)
Ana Rita Pereira, Andreas Lipphaus, Mert Ergin, Sahar Salehi, Dominic Gehweiler, Maximilian Rudert, Jan Hansmann, Marietta Herrmann
ABSTRACT

In bone tissue engineering, the design of in vitro models able to recreate both the chemical composition, the structural architecture, and the overall mechanical environment of the native tissue is still often neglected. In this study, we apply a bioreactor system where human bone-marrow hMSCs are seeded in human femoral head-derived decellularized bone scaffolds and subjected to dynamic culture, i.e., shear stress induced by continuous cell culture medium perfusion at 1.7 mL/min flow rate and compressive stress by 10% uniaxial load at 1 Hz for 1 h per day. In silico modeling revealed that continuous medium flow generates a mean shear stress of 8.5 mPa sensed by hMSCs seeded on 3D bone scaffolds. Experimentally, both dynamic conditions improved cell repopulation within the scaffold and boosted ECM production compared with static controls. Early response of hMSCs to mechanical stimuli comprises evident cell shape changes and stronger integrin-mediated adhesion to the matrix. Stress-induced Col6 and SPP1 gene expression suggests an early hMSC commitment towards osteogenic lineage independent of Runx2 signaling. This study provides a foundation for exploring the early effects of external mechanical stimuli on hMSC behavior in a biologically meaningful in vitro environment, opening new opportunities to study bone development, remodeling, and pathologies.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-SPP1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
Chloroform, anhydrous, ≥99%, contains 0.5-1.0% ethanol as stabilizer
Sigma-Aldrich
Ethylenediaminetetraacetic acid disodium salt dihydrate, suitable for electrophoresis, for molecular biology, 99.0-101.0% (titration)
Sigma-Aldrich
1-Bromo-3-chloropropane, for isolation of RNA
Sigma-Aldrich
Deoxyribonuclease I from bovine pancreas, lyophilized powder, Protein ≥85 %, ≥400 Kunitz units/mg protein