Shao Zhenxing, Zhang Xin, Pi Yanbin, Yin Ling, Li La, Chen Haifeng, Zhou Chunyan, Ao Yingfang
Institute of Sports Medicine, Peking University Third Hospital, Haidian District, Beijing, 100191, People's Republic of China.
J Biomed Mater Res A. 2015 Jan;103(1):318-29. doi: 10.1002/jbm.a.35177. Epub 2014 Apr 3.
Synovium-derived mesenchymal stem cells (SMSC) have been studied for over a decade since first being successfully isolated in 2001. These cells demonstrate the most promising therapeutic efficacy for musculoskeletal regeneration of the MSC family, particularly for cartilage regeneration. However, the mobilization and transfer of MSCs to defective or damaged tissues and organs in vivo with high accuracy and efficiency has been a major problem in tissue engineering (TE). In the present study, we identified a seven amino acid peptide sequence [SMSCs-affinity peptide (LTHPRWP; L7)] through phage display technology that has a high specific affinity to SMSCs. Our analysis suggested that L7 efficiently and specifically interacted with SMSCs without any species specificity. Thereafter, L7 was covalently conjugated onto both polycaprolactone (PCL) electrospun meshes and human decalcified bone scaffolds (hDBSc) to investigate its TE applications. After 24 h coculture with human SMSCs (hSMSCs), L7-conjugated PCL electrospun meshes had significantly more adherent hSMSCs than the control group, and the cells expanded well. Similar results were obtained using hDBSs. These results suggest that the novel L7 peptide sequence has a high specific affinity to SMSCs. Covalently conjugating this peptide to either artificial polymer material (PCL mesh) or natural material (hDBS) significantly enhances the adhesion of SMSCs. This method is applicable to a wide range of potential SMSC-based TE applications, particularly to cartilage regeneration, via surface modification on various type of materials.
自2001年首次成功分离以来,滑膜间充质干细胞(SMSC)已被研究了十多年。这些细胞在间充质干细胞家族的肌肉骨骼再生方面,尤其是软骨再生方面,展现出了最具前景的治疗效果。然而,在体内将间充质干细胞高精度、高效率地动员并转移至有缺陷或受损的组织和器官一直是组织工程(TE)中的一个主要问题。在本研究中,我们通过噬菌体展示技术鉴定出了一种七氨基酸肽序列[滑膜间充质干细胞亲和肽(LTHPRWP;L7)],它对滑膜间充质干细胞具有高度特异性亲和力。我们的分析表明,L7能高效且特异性地与滑膜间充质干细胞相互作用,且无任何物种特异性。此后,将L7共价偶联到聚己内酯(PCL)电纺网和人脱钙骨支架(hDBSc)上,以研究其在组织工程中的应用。与人滑膜间充质干细胞(hSMSCs)共培养24小时后,L7偶联的PCL电纺网比对照组附着的hSMSCs明显更多,且细胞生长良好。使用人脱钙骨支架也得到了类似结果。这些结果表明,新型L7肽序列对滑膜间充质干细胞具有高度特异性亲和力。将该肽共价偶联到人工聚合物材料(PCL网)或天然材料(hDBSc)上,可显著增强滑膜间充质干细胞的黏附。这种方法适用于广泛的基于滑膜间充质干细胞的潜在组织工程应用,特别是通过对各种类型材料进行表面修饰来实现软骨再生。