Yang Shuo, Qian Zhiyong, Liu Donghua, Wen Ning, Xu Juan, Guo Ximin
Department of Stomatology, Chinese PLA General Hospital, No. 28 Fuxing Road, Beijing, 100853, China.
School of Biological Science and Medical Engineering, Beihang University, Beijing, 100191, China.
Cell Tissue Bank. 2019 Jun;20(2):209-220. doi: 10.1007/s10561-019-09760-z. Epub 2019 Mar 11.
The treatment of articular cartilage defects has become a major clinical concern. Currently, additional efforts are necessary to develop effective methods to cure this disease. In this work, we combined gene therapy with tissue engineering methods to test their effect on cartilage repair. In in vitro experiments, we obtained C-type natriuretic peptide (CNP) gene-modified bone marrow-derived mesenchymal stem cells (BMSCs) by transfection with recombinant adenovirus containing the CNP gene and revealed that CNP gene-modified BMSCs had good chondrogenic differentiation ability. By the freeze-drying method, we successfully synthesized a chitosan/silk fibroin (CS/SF) porous scaffold, which had a suitable aperture size for chondrogenesis. Then, we loaded CNP gene-modified BMSCs onto CS/SF scaffolds and tested their effect on repairing full-thickness cartilage defects in rat joints. The gross morphology and histology examination results showed that the composite of the CNP gene-modified BMSCs and CS/SF scaffolds had better repair effects than those of the other three groups at each time point. Additionally, compared to the group with BMSCs and scaffolds, we found that there was more cartilage matrix in the CNP gene-modified BMSCs and CS/SF scaffolds group. Data obtained in the present study suggest that the composite of CNP gene-modified BMSCs and CS/SF scaffolds represent promising strategies for repairing focal cartilage lesions.
关节软骨缺损的治疗已成为临床关注的重点。目前,需要进一步努力开发有效的治疗方法。在本研究中,我们将基因治疗与组织工程方法相结合,以测试其对软骨修复的效果。在体外实验中,我们通过用含C型利钠肽(CNP)基因的重组腺病毒转染,获得了CNP基因修饰的骨髓间充质干细胞(BMSCs),并发现CNP基因修饰的BMSCs具有良好的软骨分化能力。通过冷冻干燥法,我们成功合成了壳聚糖/丝素蛋白(CS/SF)多孔支架,其孔径大小适合软骨生成。然后,我们将CNP基因修饰的BMSCs接种到CS/SF支架上,并测试其对大鼠关节全层软骨缺损修复的效果。大体形态和组织学检查结果表明,在各个时间点,CNP基因修饰的BMSCs与CS/SF支架的复合物比其他三组具有更好的修复效果。此外,与BMSCs和支架组相比,我们发现在CNP基因修饰的BMSCs与CS/SF支架组中有更多的软骨基质。本研究获得的数据表明,CNP基因修饰的BMSCs与CS/SF支架的复合物是修复局灶性软骨损伤的有前景的策略。