我校西南医院创伤关节外科杨柳教授团队在Bioactive Materials上发表研究成果——弹性蛋白原通过促进髌下脂肪垫来源间充质干细胞早期粘附延缓骨关节炎疾
发布人:wuph 发布时间:5/31/2022 11:51:39 AM  浏览次数:594次
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弹性蛋白原通过促进髌下脂肪垫来源间充质干细胞早期粘附延缓骨关节炎疾病进展  

杨君君 龚啸元 杨柳

 

骨关节炎(OsteoarthritisOA)是最常见的累及膝、髋和踝等关节的渐进性退行疾病,尚无有效的干预手段,目前临床上的治疗手段仅减轻患者症状,无法彻底延缓疾病进程。随着再生医学的发展,间充质干细胞(Mesenchymal stem cellMSCs)在OA的临床治疗中展现出良好的应用前景。然而,MSCs受关节腔内复杂力学环境影响,早期粘附定居能力不足,容易引发MSCs失巢凋亡,进而影响其发挥生物学效应。因此,如何提升MSCs在关节腔内的早期粘附是软骨再生医学中的关键问题与技术难点。

弹性蛋白原 (TropoelastinTE) 是弹性纤维组织中提供结构支撑并赋予其韧性和弹性的重要胞外基质成分。在本研究中,团队首次将TE作为MSCIPFP注射的混悬剂,并与经典的MSCs注射溶剂生理盐水(NS)、透明质酸(HA)和富含血小板的血浆(PRP)进行比较,观察TE对髌下脂肪垫间充质干细胞(MSCIPFP)生物学行为(黏附、迁移、分化与旁分泌),MSCIPFP在关节腔内的分布-存活;及体内延缓OA进程的调控作用。研究团队利用体外细胞培养与人体组织块模型,发现TE通过活化Integrin β1/ERK/Vinculin通路促进MSCIPFP粘附、迁移及成软骨分化。在间接共培养系统中,TE能够增强MSCIPFP旁分泌作用,并上调骨关节炎软骨细胞(Osteoarthritic chondrocytesOACs)软骨基质合成。体内研究模型结果显示,TE作为关节腔注射混悬剂可有效提升MSCIPFP关节腔早期存活,并有效地延缓大鼠OA的进程。研究团队的发现为MSC关节内注射治疗OA提供了一种新的方法策略。

上述研究成果在陆军军医大学西南医院创伤关节外科杨柳教授、龚啸元副研究员与重庆医科大学医学信息学院陈诚研究员的指导下,主要由陆军军医大学2018级博士研究生杨君君与陆军军医大学西南医院创伤关节外科王鑫研究实习员共同完成,受重庆市英才计划(4246ZJ1)与重庆市教委基金(KJQN202000427)资助,于202109月在线发表于Bioactive MaterialsIF=14.593)期刊上。

 

附:英文摘要

Intra-articular injection of mesenchymal stem cells (MSCs) is a promising strategy for osteoarthritis (OA) treatment. However, more and more studies reveal that the injected MSCs have poor adhesion, migration, and survival in the joint cavity. A recent study shows that tropoelastin (TE) regulates adhesion, proliferation and phenotypic maintenance of MSCs as a soluble additive, indicating that TE could promote MSCs-homing in regenerative medicine. In this study, we used TE as injection medium, and compared it with classic media in MSCs intra-articular injection such as normal saline (NS), hyaluronic acid (HA), and platelet-rich plasma (PRP). We found that TE could effectively improve adhesion, migration, chondrogenic differentiation of infrapatellar fat pad MSCs (IPFP-MSCs) and enhance matrix synthesis of osteoarthritic chondrocytes (OACs) in indirect-coculture system. Moreover, TE could significantly enhance IPFP-MSCs adhesion via activation of integrin β1, ERK1/2 and vinculin (VCL) in vitro. In addition, intra-articular injection of TE-IPFP MSCs suspension resulted in a short-term increase in survival rate of IPFP-MSCs and better histology scores of rat joint tissues. Inhibition of integrin β1 or ERK1/2 attenuated the protective effect of TE-IPFP MSCs suspension in vivo. In conclusion, TE promotes performance of IPFP-MSCs and protects knee cartilage from damage in OA through enhancement of cell adhesion and activation of integrin β1/ERK/VCL pathway. Our findings may provide new insights in MSCs intra-articular injection for OA treatment.

 


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