Magnitude‐dependent and inversely‐related osteogenic/chondrogenic differentiation of human mesenchymal stem cells under dynamic compressive strain
0301 basic medicine
Compressive Strength
1.1 Normal biological development and functioning
Cells
Clinical Sciences
Medical Physiology
Biomedical Engineering
Bioengineering
Regenerative Medicine
Stress
osteogenesis
03 medical and health sciences
Stem Cell Research - Nonembryonic - Human
Underpinning research
human mesenchymal stem cell
Osteogenesis
electrospun scaffold
chondrogenesis
Humans
Tomography
dynamic compression
Cells, Cultured
Cultured
Tissue Scaffolds
Cell Differentiation
Mesenchymal Stem Cells
differentiation
Stem Cell Research
Mechanical
Extracellular Matrix
Optical Coherence
Musculoskeletal
Stem Cell Research - Nonembryonic - Non-Human
Stress, Mechanical
Chondrogenesis
Tomography, Optical Coherence
DOI:
10.1002/term.2332
Publication Date:
2016-09-30T02:08:25Z
AUTHORS (6)
ABSTRACT
Biomechanical forces have been shown to significantly affect tissue development, morphogenesis, pathogenesis and healing, especially in orthopaedic tissues. Such biological processes are critically related to the differentiation of human mesenchymal stem cells (hMSCs). However, the mechanistic details regarding how mechanical forces direct MSC differentiation and subsequent tissue formation are still elusive. Electrospun three-dimensional scaffolds were used to culture and subject hMSCs to various magnitudes of dynamic compressive strains at 5, 10, 15 or 20% (ε = 0.05, 0.10, 0.15, 0.20) at a frequency of 1 Hz for 2 h daily for up to 28 days in osteogenic media. Gene expression of chondrogenic markers (ACAN, COL2A1, SOX9) and glycosaminoglycan (GAG) synthesis were upregulated in response to the increased magnitudes of compressive strain, whereas osteogenic markers (COL1A1, SPARC, RUNX2) and calcium deposition had noticeable decreases by compressive loading in a magnitude-dependent manner. Dynamic mechanical analysis showed enhanced viscoelastic modulus with respect to the increased dynamic strain peaking at 15%, which coincides with the maximal GAG synthesis. Furthermore, polarization-sensitive optical coherence tomography revealed that mechanical loading enhanced the alignment of extracellular matrix to the greatest level by 15% strain as well. Overall, we show that the degree of differentiation of hMSCs towards osteogenic or chondrogenic lineage is inversely related, and it depends on the magnitude of dynamic compressive strain. These results demonstrate that multiphenotypic differentiation of hMSCs can be controlled by varying the strain regimens, providing a novel strategy to modulate differentiation specification and tissue morphogenesis. Copyright © 2016 John Wiley & Sons, Ltd.
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