The effect of matrix stiffness on mesenchymal stem cell differentiation in a 3D thixotropic gel.
Recent studies have demonstrated the effect of matrix stiffness on the phenotype and differentiation pathway of mesenchymal stem cells (MSCs). MSCs differentiated into neural, myogenic or osteogenic phenotypes depending on whether they were cultured on two-dimensional (2D) substrates of elastic moduli in the lower (0.1-1 kPa), intermediate (8-17 kPa) or higher ranges (34 kPa). In this study, MSCs were cultured in thixotropic gels of varying rheological properties, and similar results were found for the three-dimensional (3D) culture as for the previous findings in 2D culture. For the 3D cell cultures in thixotropic gels, the liquefaction stress (tau(y)), the minimum shear stress required to liquefy the gel, was used to characterize the matrix stiffness. The highest expressions of neural (ENO2), myogenic (MYOG) and osteogenic (Runx2, OC) transcription factors were obtained for gels with tau(y) of 7, 25 and 75 Pa, respectively. Immobilization of the cell-adhesion peptide, RGD, promoted both proliferation and differentiation of MSCs, especially for the case of the stiffer gels (>75 Pa). This study demonstrated the usefulness of thixotropic gels for 3D cell culture studies, as well as the use of tau(y) as an effective measure of matrix stiffness that could be correlated to MSC differentiation.
Pek
Y Shona
YS
Institute of Bioengineering and Nanotechnology, The Nanos #04-01, Singapore.
Wan
Andrew C A
AC
Ying
Jackie Y
JY
D018929:Cell Culture Techniques / Q000295:instrumentation / Q000379:methods; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D048430:Cell Shape; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000737:chemistry* / Q000378:metabolism; D005782:Gels / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008422:Materials Testing; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000502:physiology*; D011092:Polyethylene Glycols / Q000737:chemistry; D012822:Silicon Dioxide / Q000737:chemistry; D054457:Tissue Scaffolds; D014783:Viscosity
D005782:Gels; D011092:Polyethylene Glycols; D012822:Silicon Dioxide