title: Effects of substrate stiffness on adipogenic and osteogenic differentiation of human mesenchymal stem cells.
abstract: Substrate mechanical properties, in addition to biochemical signals, have been shown to modulate cell phenotype. In this study, we inspected the effects of substrate stiffness on human mesenchymal stem cells (hMSCs) derived from adult human bone marrow differentiation into adipogenic and osteogenic cells. A chemically modified extracellular matrix derived and highly biocompatible hydrogel, based on thiol functionalized hyaluronic acid (HA-SH) and thiol functionalized recombinant human gelatin (Gtn-SH), which can be crosslinked by poly (ethylene glycol) tetra-acrylate (PEGTA), was used as a model system. The stiffness of the hydrogel was controlled by adjusting the crosslinking density. Human bone marrow MSCs were cultured on the hydrogels with different stiffness under adipogenic and osteogenic conditions. Oil Red O staining and F-actin staining were applied to assess the change of cell morphologies under adipogenic and osteogenic differentiation, respectively. Gene expression of cells was determined with reverse transcription polymerase chain reaction (RT-PCR) as a function of hydrogel stiffness. Results support the hypothesis that adipogenic and osteogenic differentiation of hMSCs are inclined to occur on substrate with stiffness similar to their in vivo microenvironments.
authors.affiliation: Department of Orthopedic Surgery, The General Hospital of Chinese People's Liberation Army (301 hospital), Beijing, 100853, PR China; Department of Orthopedic Surgery; Beijing Aerospace General Hospital, Beijing, 100076, PR China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Clemson -MUSC Bioengineering Program, Department of Bioengineering, Clemson University, Charleston, SC 29425, USA.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Li
authors.affiliation: Clemson -MUSC Bioengineering Program, Department of Bioengineering, Clemson University, Charleston, SC 29425, USA.
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Liu
authors.affiliation: Clemson -MUSC Bioengineering Program, Department of Bioengineering, Clemson University, Charleston, SC 29425, USA; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Clemson -MUSC Bioengineering Program, Department of Bioengineering, Clemson University, Charleston, SC 29425, USA; Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, USA; Department of Orthopedic Surgery, Medical University of South Carolina, Charleston, SC 29425, USA; East Hospital, Tongji University School of Medicine, Shanghai, 200120, PR China; The Institute for Biomedical Engineering and Nano Science, Tongji University School of Medicine, Shanghai, 200092, PR China. Electronic address: xjwen@clemson.edu.
authors.forename: Xuejun
authors.initials: X
authors.lastname: Wen
mesh_terms: D050156:Adipogenesis / Q000187:drug effects; D018929:Cell Culture Techniques / Q000295:instrumentation; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D005780:Gelatin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000166:cytology*; D010012:Osteogenesis / Q000187:drug effects; D011092:Polyethylene Glycols / Q000737:chemistry; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics
chemical_list: D020100:Hydrogels; D011994:Recombinant Proteins; C521883:poly(ethylene glycol) tetra-acrylate; D011092:Polyethylene Glycols; D005780:Gelatin; D006820:Hyaluronic Acid
keywords: Differentiation; Hydrogel; Mechanical property; Mesenchymal stem cells