COMP-lex Mechanics

Tintut, Yin; Demer, Linda L.

doi:10.1161/circresaha.116.309121

Cited by 2 publications

(2 citation statements)

References 28 publications

(33 reference statements)

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“…3 ). These changes in cytoskeletal structure may also stimulate mechanotransduction 68 , 69 , mimicking early chondrogenic condensation by changing both cell shape and ECM structure, resulting in increases in cell–cell interactions via β-catenin and upregulation of pro-chondrogenic signaling molecules BMP2 (regulator of cellular condensation) 70 and COMP (regulator of collagen accumulation and ECM assembly) 71 prior to chondrogenic induction.…”

Section: Discussionmentioning

confidence: 99%

“…proteoglycan, aggrecan, and type II collagen content), ECM deposition (as seen in differentiating 3D contracted sheets) is also associated with hyaline chondrogenic differentiation 14 . The cytoskeletal reorganization within 3D contracted cell sheets prior to chondrogenic induction upregulates COMP and BMP2, which are directly associated with ECM assembly and collagen accumulation 71 , 73 , resulting in significantly more ECM deposition in the 3D cell sheets than in the 2D cultures after chondrogenic induction. 3D cell sheets, generated from spontaneous contraction upon temperature-mediated detachment from culture surfaces, are initially cell-dense structures; however, ECM deposition that significantly increases 3D cell sheet thickness during chondrogenesis decreases the construct’s overall cellular density.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Fabrication of hyaline-like cartilage constructs using mesenchymal stem cell sheets

Thorp

Kim

Kondō

et al. 2020

Sci Rep

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Cell and tissue engineering approaches for articular cartilage regeneration increasingly focus on mesenchymal stem cells (MSCs) as allogeneic cell sources, based on availability and innate chondrogenic potential. Many MSCs exhibit chondrogenic potential as three-dimensional (3D) cultures (i.e. pellets and seeded biomaterial scaffolds) in vitro; however, these constructs present engraftment, biocompatibility, and cell functionality limitations in vivo. Cell sheet technology maintains cell functionality as scaffold-free constructs while enabling direct cell transplantation from in vitro culture to targeted sites in vivo. The present study aims to develop transplantable hyaline-like cartilage constructs by stimulating MSC chondrogenic differentiation as cell sheets. To achieve this goal, 3D MSC sheets are prepared, exploiting spontaneous post-detachment cell sheet contraction, and chondrogenically induced. Results support 3D MSC sheets’ chondrogenic differentiation to hyaline cartilage in vitro via post-contraction cytoskeletal reorganization and structural transformations. These 3D cell sheets’ initial thickness and cellular densities may also modulate MSC-derived chondrocyte hypertrophy in vitro. Furthermore, chondrogenically differentiated cell sheets adhere directly to cartilage surfaces via retention of adhesion molecules while maintaining the cell sheets’ characteristics. Together, these data support the utility of cell sheet technology for fabricating scaffold-free, hyaline-like cartilage constructs from MSCs for future transplantable articular cartilage regeneration therapies.

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Section: Discussionmentioning

confidence: 99%