Differential effects of EGF and TGF-beta1 on fibroblast activity in fibrin-based tissue equivalents
UMass Chan Affiliations
Graduate School of Biomedical SciencesDocument Type
Journal ArticlePublication Date
2007-03-10Keywords
Cell Culture Techniques; Cell Proliferation; Cells, Cultured; Compressive Strength; Connective Tissue; Drug Combinations; Elasticity; Epidermal Growth Factor; Fibrin; Foreskin; Humans; Male; Tissue Engineering; Transforming Growth Factor beta1Life Sciences
Medicine and Health Sciences
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Show full item recordAbstract
Transforming growth factor-beta1 (TGF-beta1) is commonly used to promote matrix production for engineered tissues in vitro, yet it also enhances fibroblast contractility. For applications where contraction is undesirable, we hypothesized that epidermal growth factor (EGF) would yield equivalent mechanical properties without enhancing contractility. In this study, the response of human dermal fibroblasts to EGF (5 ng/mL) and TGF-beta1 (5 ng/mL) was determined within hemispheric fibrin-based gels by assessing matrix compaction and strength, cell number, collagen production, and contractility. After 3 weeks, both cytokines enhanced compaction relative to controls, and EGF roughly doubled matrix strength over controls and TGF-beta1-treated samples. TGF-beta1 induced alpha-smooth muscle actin (alphaSMA) expression whereas EGF did not. TGF-beta1 also increased retraction following substrate release while EGF reduced retraction. Treatment with cytochalasin D revealed that, regardless of growth factor, approximately 10% of the total retraction was due to residual matrix stress accumulated during cell-mediated remodeling. EGF increased the cell number by 17%, whereas TGF-beta1 decreased the cell number by 63% relative to controls. EGF and TGF-beta1 stimulated greater collagen content than controls by 49% and 33%, respectively. These data suggest that EGF may be an attractive alternative to TGF-beta1 for engineering fibrin-based connective tissue substitutes with adequate strength and minimal tissue contractility.Source
Tissue Eng. 2007 Apr;13(4):799-807. Link to article on publisher's siteDOI
10.1089/ten.2006.0206Permanent Link to this Item
http://hdl.handle.net/20.500.14038/33762PubMed ID
17346099Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1089/ten.2006.0206