Abstract
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.
Highlights
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
Cultured human bone marrowderived mesenchymal stem cell sheets spontaneously contracted after detachment from temperatureresponsive culture dishes (Fig. 2)
Cultured human bone marrowderived mesenchymal stem cell (hBMSC) sheet cytoskeletal arrangements were observed with phalloidin (F-actin) fluorescent staining, and nuclei were identified by DAPI (Fig. 3a,b)
Summary
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. 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. Extensive work has been reported for tailoring scaffold materials, such as collagens, alginates, hyaluronic acid, or PGA/PLA, to accommodate cells and promote more homogenous chondrogenic d ifferentiation[23,29,30] Even when these cell-seeded scaffolds achieve in vitro chondrogenic differentiation, the presence of scaffold materials or necessary exogenous adhesives inhibit direct communication between transplanted cells and the target tissue, resulting in poor functional regeneration post-implantation[9,11,23]. As a next-generation approach, this study represents a “back-to-bench” strategy to further build upon established cell sheet precedent and support development of future cartilage regeneration therapies
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