title: Enhancement of tenogenic differentiation of human adipose stem cells by tendon-derived extracellular matrix.
abstract: Mesenchymal stem cells (MSCs) have gained increasing research interest for their potential in improving healing and regeneration of injured tendon tissues. Developing functional three-dimensional (3D) scaffolds to promote MSC proliferation and differentiation is a critical requirement in tendon tissue engineering. Tendon extracellular matrix has been shown to maintain the tenogenic potential of tendon stem cells and stimulate tenogenesis of human adipose stem cells (hASCs) in 2D culture. This study aims at characterizing the biological composition of urea-extracted fraction of tendon ECM (tECM) and its tenogenic effect on hASCs cultured in a 3D collagen scaffold under uniaxial tension. The tECM obtained was cell-free and rich in ECM proteins. hASCs seeded in tECM-supplemented scaffold exhibited significantly increased proliferation and tenogenic differentiation. The presence of tECM also greatly suppressed the osteogenic differentiation of hASCs triggered by uniaxial tension. In addition, tECM-supplemented constructs displayed enhanced mechanical strength, accompanied by reduced expression and activity of MMPs in the seeded hASCs, indicating a regulatory activity of tECM in cell-mediated scaffold remodeling. These findings support the utility of tECM in creating bio-functional scaffolds for tendon tissue engineering.
authors.affiliation: Center for Cellular and Molecular Engineering, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15219, USA; Department of Bioengineering, University of Pittsburgh Swanson School of Engineering, Pittsburgh, PA 15219, USA.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.forename: Benjamin B
authors.initials: BB
authors.lastname: Rothrauff
authors.forename: Hang
authors.initials: H
authors.lastname: Lin
authors.forename: Riccardo
authors.initials: R
authors.lastname: Gottardi
authors.forename: Peter G
authors.initials: PG
authors.lastname: Alexander
authors.forename: Rocky S
authors.initials: RS
authors.lastname: Tuan
mesh_terms: D017667:Adipocytes / Q000166:cytology; D000273:Adipose Tissue / Q000166:cytology*; D000328:Adult; D000818:Animals; D002417:Cattle; D002454:Cell Differentiation; D002470:Cell Survival; D003094:Collagen / Q000737:chemistry; D005109:Extracellular Matrix / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D006801:Humans; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D013710:Tendons / Q000737:chemistry / Q000166:cytology*; D023822:Tissue Engineering; D054457:Tissue Scaffolds / Q000737:chemistry*
chemical_list: D003094:Collagen
keywords: Adipose stem cells; Collagen scaffold; Decellularized matrix; Tendon regeneration; Tenogenesis
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