1 Institute of Biomedical and Pharmaceutical Technology, Fuzhou University , Fuzhou, P.R. China .
2 Agricultural Product Quality Institute, Fujian Agriculture and Forestry University , Fuzhou, P.R. China .
Tissue Eng Part A. 2018 Jun;24(11-12):990-1000. doi: 10.1089/ten.TEA.2017.0162. Epub 2018 Jan 25.
Articular cartilage has poor capability of regeneration due to the avascular surrounding and low metabolic activity. Kartogenin (KGN), an emerging nonprotein heterocyclic compound, was screened to stimulate chondrogenic differentiation of bone mesenchymal stem cells (BMSCs). Coculturing BMSCs and chondrocytes was reported to overcome the shortcomings of forming fibroblastic and hypertrophic cartilages. In this study, KGN was incorporated into the Col-Tgel hydrogel to form a Gel/Cell/KGN complex, which fabricated an appropriate microenvironment for effective cartilage regeneration of BMSCs and/or chondrocytes. The complexes that incorporated KGN, BMSCs, and chondrocytes achieved higher lubricin expression and extracellular matrix production, such as characteristic glycosaminoglycans (GAGs) and collagen type II (COL II), compared to the monocultures of BMSCs or chondrocytes in vitro. The complexes compounding KGN, BMSCs, and chondrocytes (at an optimal ratio in the in vitro experiment) were transplanted into rat models to evaluate the repair effects. Our results suggested that the interaction between BMSCs and chondrocytes can substitute the use of growth factors to some degree and indicated the role of KGN in chondrogenesis induction. Besides, it is the first time (to our knowledge) that the expression of lubricin was found to be delayed in the coculture of mixed cells comparing with GAGs and COL II, which could be significant in cartilage tissue engineering.
关节软骨由于其周围缺乏血管和低代谢活性,再生能力较差。Kartogenin(KGN)是一种新兴的非蛋白杂环化合物,被筛选出来以刺激骨髓间充质干细胞(BMSCs)的软骨分化。有报道称,共培养 BMSCs 和软骨细胞可以克服形成纤维性和肥大性软骨的缺点。在本研究中,KGN 被掺入 Col-Tgel 水凝胶中以形成 Gel/Cell/KGN 复合物,为 BMSCs 和/或软骨细胞的有效软骨再生构建了适当的微环境。与体外 BMSCs 或软骨细胞的单一培养相比,掺入 KGN、BMSCs 和软骨细胞的复合物实现了更高的润滑素表达和细胞外基质产生,如特征性糖胺聚糖(GAGs)和 II 型胶原(COL II)。在体外实验中优化比例复合 KGN、BMSCs 和软骨细胞的复合物被移植到大鼠模型中以评估修复效果。我们的结果表明,BMSCs 和软骨细胞之间的相互作用在某种程度上可以替代生长因子的使用,并表明 KGN 在诱导软骨形成中的作用。此外,这是首次(据我们所知)发现与 GAGs 和 COL II 相比,混合细胞共培养中润滑素的表达延迟,这在软骨组织工程中可能具有重要意义。