Zhang Feng, Su Kai, Fang Yu, Sandhya Swaminathan, Wang Dong-An
Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, 637457, Republic of Singapore.
J Tissue Eng Regen Med. 2015 Jan;9(1):77-84. doi: 10.1002/term.1641. Epub 2012 Nov 20.
To regenerate articular cartilage tissue from degeneration and trauma, synovial mesenchymal stem cells (SMSCs) were used in this study as therapeutic progenitor cells to induce therapeutic chondrogenesis. To accomplish this, chondrocytes pre-transduced with adenoviral vectors carrying the transforming growth factor (TGF) β3 gene were selected as transgenic companion cells and co-cultured side-by-side with SMSCs in a 3D environment to provide chondrogenic growth factors in situ. We adopted a mixed co-culture strategy for this purpose. Transgenic delivery of TGF-β3 in chondrocytes was performed via recombinant adenoviral vectors. The mixed co-culture of SMSCs and transgenic chondrocytes was produced in alginate gel constructs. Gene expression in both SMSCs and chondrocytes were characterized. Biochemical assays in vitro and in vivo showed that release of TGF-ß3 from transgenic chondrocytes not only induced SMSC differentiation into chondrocytic cells but also preserved the chondrocytic phenotype of chondrocytes from suspected dedifferentiation. As a result, this mixed co-culture strategy in conjunction with TGF-ß3 gene delivery could be a promising approach in cartilage tissue engineering.
为了从退变和创伤中再生关节软骨组织,本研究使用滑膜间充质干细胞(SMSC)作为治疗性祖细胞来诱导治疗性软骨形成。为此,选择用携带转化生长因子(TGF)β3基因的腺病毒载体预转导的软骨细胞作为转基因伴细胞,并在三维环境中与SMSC并排共培养,以原位提供软骨形成生长因子。为此我们采用了混合共培养策略。通过重组腺病毒载体在软骨细胞中进行TGF-β3的转基因递送。SMSC与转基因软骨细胞的混合共培养在藻酸盐凝胶构建体中进行。对SMSC和软骨细胞中的基因表达进行了表征。体外和体内的生化分析表明,转基因软骨细胞释放的TGF-β3不仅诱导SMSC分化为软骨细胞,还能保护软骨细胞的软骨细胞表型不发生疑似去分化。因此,这种混合共培养策略结合TGF-β3基因递送可能是软骨组织工程中一种有前景的方法。