Effect of mechanical loading and substrate elasticity on the osteogenic and adipogenic differentiation of mesenchymal stem cells

Autor: X. Frank Walboomers, John A. Jansen, Min Bao, Hatice Imran Gungordu, Sander C.G. Leeuwenburgh, Sjoerd van Helvert
Rok vydání: 2019
Předmět:
Cancer development and immune defence Radboud Institute for Molecular Life Sciences [Radboudumc 2]
Cellular differentiation
0206 medical engineering
Biomedical Engineering
Acrylic Resins
Medicine (miscellaneous)
02 engineering and technology
Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9]
Biomaterials
Extracellular matrix
03 medical and health sciences
Osteogenesis
Extracellular
Animals
Dimethylpolysiloxanes
Elasticity (economics)
030304 developmental biology
0303 health sciences
Adipogenesis
Chemistry
Mesenchymal stem cell
Biomaterial
Cell Differentiation
Mesenchymal Stem Cells
020601 biomedical engineering
Elasticity
Rats
Reconstructive and regenerative medicine Radboud Institute for Molecular Life Sciences [Radboudumc 10]
Biophysics
Alkaline phosphatase
Physical Organic Chemistry
Zdroj: Journal of Tissue Engineering and Regenerative Medicine, 13, 12, pp. 2279-2290
Journal of Tissue Engineering and Regenerative Medicine, 13, 2279-2290
ISSN: 1932-6254
DOI: 10.1002/term.2956
Popis: Contains fulltext : 215424.pdf (Author’s version postprint ) (Open Access) Mesenchymal stem cells (MSCs) are highly sensitive to biomechanics of their extracellular environment. Generally, a higher elasticity of culture substrates can drive cells into the osteogenic lineage, whereas low substrate elasticity results in adipogenesis. Applied mechanical loading by cyclic strain is another major variable influencing cell fate. Yet, little is known about the simultaneous effect of both cues. Therefore, the present study investigated the relative importance of both cues on differentiation. MSCs were cultured in an osteogenic and also an adipogenic environment on soft polyacrylamide (PAAm; E = 23 +/- 0.3 kPa), stiff PAAm (111 +/- 2 kPa), and polydimethylsiloxane (PDMS; E = 1,5 +/- 0.07 MPa) either unstrained or with 8% cyclic strain at 1 Hz. Without strain, the relative expression of the early osteogenic marker alkaline phosphatase (ALP) was significantly higher (78%) on PDMS than on both PAAm. With 8% cyclic strain, ALP expression increased for all groups in comparison with unstrained controls. The highest increase was observed for the soft PAAm by 36%. Moreover, relative oil red O (ORO) expression-indicating adipogenesis-was the highest for unstrained soft PAAm. On the other hand, the percentage of ORO positive cells significantly decreased by 57% and 69% for soft and stiff PAAm when strained. In conclusion, biomaterial elasticity and mechanical loading can act simultaneously on cell differentiation. Substrate elasticity is an important factor, regulating the differentiation, but cyclic strain can drive MSCs towards the osteogenesis even on the softest substrate. As such, the osteogenic effect of mechanical loading can overrule the adipogenic effect of soft substrates, thereby acting as an inhibitor.
Databáze: OpenAIRE