Osteogenic and Adipogenic Differentiation of Mesenchymal Stem Cells in Gelatin Solutions of Different Viscosities

Abstract

Accumulating evidence indicates that stem cell fate can be regulated by mechanical properties of the extracellular matrix. Most studies have focused onthe influence of matrix elasticity and viscoelasticity on stem cell differentiation. However, how matrix viscosity affects stem cell differentiation has been overlooked. In this study, a biphasic gelatin solution/hydrogel system is used for 3D culture of human bone marrow-derived mesenchymal stem cells (MSCs) to investigate the influence of gelatin solution viscosity on simultaneous osteogenic and adipogenic differentiation at the same culture condition. Gelatin solution promotes cell proliferation, while its promotive effect decreases with the increase of viscosity. The influence of viscosity on osteogenic and adipogenic differentiation of MSCs shows opposite trends. A high-viscosity gelatin solution results in an increase of alkaline phosphatase (ALP) activity, calcium deposition, and expression of osteogenesis-related genes. On the other hand, in a low-viscosity gelatin solution, a lot of lipid vacuoles are formed and adipogenesis-related genes are highly expressed. The results indicate high viscosity is beneficial for osteogenic differentiation, while low viscosity is beneficial for adipogenic differentiation. These findings suggest the importance of matrix viscosity on stem cell differentiation in 3D microenvironments.

Engineering cartilage graft using mesenchymal stem cell laden polyacrylamide-galactoxyloglucan hydrogel for transplantation

“…Softer elastomer (2.5-5 kPa) scaffolds enhance chondrogenic and adipogenic differentiation of MSCs, while stiffer (11-30kPa) ones promote their osteogenic differentiation. [25][26][27] The complex modulus of GS after gelling was found to be 3.8 Â 10 2 Pa, which was significantly higher than the modulus during the preparation i.e. 2.2 Â 10 1 Pa. 15 This confirms the role of stiffness of hydrogel for stem cell differentiation.…”

Effect of extracellular matrix proteins on the differentiation of human pluripotent stem cells into mesenchymal stem cells

“…This can be explained by the fact that hMSCs prefer to differentiate into osteoblasts on stiff surfaces, such as TCP dishes and dishes coated with other ECM proteins, but not on the soft hydrogel surface of MAT-coated dishes. 25,54–56…”

Colonization versus encapsulation in cell-laden materials design: porosity and process biocompatibility determine cellularization pathways

“…Bioprinted hydrogels have also been used for osteogenic [287] and chondrogenic [288] differentiation. However, reproducing cell differentiation in threedimensional cell culture is a delicate process and differentiation can be hampered [289] or shifted into other lineages [290][291][292]. In addition, cell differentiation can be achieved combining hydrogels with three-dimensionally printed constructs for bone repair [293], or using other biofabrication techniques such as alginate fibres produced in a microfluidic platform to obtain insulin-producing cells for diabetes treatment [294].…”