title: Enhanced cartilage formation via three-dimensional cell engineering of human adipose-derived stem cells.
abstract: Autologous chondrocyte implantation is an effective treatment for damaged articular cartilage. However, this method involves surgical procedures that may cause further cartilage degeneration, and in vitro expansion of chondrocytes can result in dedifferentiation. Adipose-derived stem cells (ADSCs) may be an alternative autologous cell source for cartilage regeneration. In this study, we developed an effective method for large-scale in vitro chondrogenic differentiation, which is the procedure that would be required for clinical applications, and the subsequent in vivo cartilage formation of human ADSCs (hADSCs). The spheroid formation and chondrogenic differentiation of hADSCs were induced on a large scale by culturing hADSCs in three-dimensional suspension bioreactors (spinner flasks). In vitro chondrogenic differentiation of hADSCs was enhanced by a spheroid culture compared with a monolayer culture. The enhanced chondrogenesis was probably attributable to hypoxia-related cascades and enhanced cell-cell interactions in hADSC spheroids. On hADSCs loading in fibrin gel and transplantation into subcutaneous space of athymic mice for 4 weeks, the in vivo cartilage formation was enhanced by the transplantation of spheroid-cultured hADSCs compared with that of monolayer-cultured hADSCs. This study shows that the spheroid culture may be an effective method for large-scale in vitro chondrogenic differentiation of hADSCs and subsequent in vivo cartilage formation.
authors.affiliation: School of Chemical and Biological Engineering, Seoul National University, Seoul, Republic of Korea.
authors.forename: Hee Hun
authors.initials: HH
authors.lastname: Yoon
authors.forename: Suk Ho
authors.initials: SH
authors.lastname: Bhang
authors.forename: Jung-Youn
authors.initials: JY
authors.lastname: Shin
authors.forename: Jaehoon
authors.initials: J
authors.lastname: Shin
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Kim
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D019149:Bioreactors; D015153:Blotting, Western; D002356:Cartilage / Q000166:cytology*; D060846:Cell Engineering / Q000379:methods*; D020219:Chondrogenesis / Q000502:physiology; D006801:Humans; D007150:Immunohistochemistry; D018625:Microscopy, Atomic Force; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology*; D023822:Tissue Engineering / Q000379:methods*