Ectopic neocartilage formation from predifferentiated human adipose derived stem cells induced by adenoviral-mediated transfer of hTGF beta2

• Published in: Biomaterials 2007-07, Vol.28 (19), p.2994-3003
• Main Authors: Jin, Xiao bing, Sun, Yong sheng, Zhang, Ke, Wang, Jing, Shi, Tai ping, Ju, Xiao dong, Lou, Si quan
• Format: Article
• Language: English
• Subjects: Adenoviridae - genetics; Adenoviridae - metabolism; Adenovirus; Adipose Tissue - cytology; Advanced Basic Science; Aged; Alginate; Alginates - chemistry; Alginates - metabolism; Animals; Biocompatible Materials - chemistry; Biocompatible Materials - metabolism; Cartilage - cytology; Cartilage - physiology; Cell Differentiation - physiology; Cells, Cultured; Chondrogenesis - physiology; Chondrogenic; Dentistry; Genetic Vectors - genetics; Genetic Vectors - metabolism; Glucuronic Acid - chemistry; Glucuronic Acid - metabolism; Hexuronic Acids - chemistry; Hexuronic Acids - metabolism; Human transforming beta 2 (hTGF beta2); Humans; Lactic Acid - chemistry; Lactic Acid - metabolism; Mice; Mice, Inbred BALB C; Mice, Nude; Middle Aged; PLGA; Polyglycolic Acid - chemistry; Polyglycolic Acid - metabolism; Polymers - chemistry; Polymers - metabolism; Stem Cells - cytology; Stem Cells - physiology; Tissue engineering; Tissue Engineering - methods; Transforming Growth Factor beta2 - genetics; Transforming Growth Factor beta2 - metabolism
• ISSN: 0142-9612; 1878-5905
• DOI: 10.1016/j.biomaterials.2007.03.002

Abstract Chondrogenic potential of human adipose derived stem cells (hASCs) makes them a possible source of seeding cells for cartilage tissue engineering. In this study, chondrogenic differentiation of hASCs induced by transduction with replication-deficient adenovirus carrying human transforming growth factor beta2 (Ad5-hTGF beta2) was demonstrated by RT-PCR, immunohistochemistry staining, biochemical and western blot analysis. To evaluate if the in vitro differentiated hASCs could keep their chondrocytic phenotype and produce neo-cartilage in vivo, predifferentiated hASCs were seeded in different scaffolds and implanted in subcutaneous pockets on the dorsum of nude mice. After 4 and 12 weeks culture in vivo, specimens were harvested and examined by histological and immunohistochemical analysis, cartilage-like tissue formation was only found in alginate gel and PLGA/alginate compound groups, in PLGA group, fibrous tissues and angiogenesis ingrowth were observed. These findings demonstrated that adenovirus-mediated hTGF beta2 gene transfer could induce hASCs into a chondrogenic lineage in vitro, however, this predifferentiation did not guarantee ectopic cartilage formation in vivo unless appropriate three-dimensional scaffolds were used as the cell carry vehicles.