Center for Stem Cell and Tissue Engineering, Department of Orthopedic Surgery, Second Affiliated Hospital, and Department of Sports Medicine, School of Medicine, Zhejiang University, Hangzhou, People's Republic of China; Department of Biosystems Science and Engineering, Eidgenössische Technische Hochschule, Zurich, Switzerland.
Stem Cells Transl Med. 2014 Mar;3(3):387-94. doi: 10.5966/sctm.2012-0170. Epub 2014 Jan 21.
Meniscus injury is frequently encountered in clinical practice. Current surgical therapy involving partial or complete meniscectomy relieves pain in the short-term but often leads to osteoarthritis (OA) in the long-term. In this study, we report a new strategy of articular cartilage protection by intra-articular injection of novel human meniscus stem/progenitor cells (hMeSPCs). We found that hMeSPCs displayed both mesenchymal stem cell characteristics and high expression levels of collagen II. In the rat meniscus injury model, hMeSPC transplantation not only led to more neo-tissue formation and better-defined shape but also resulted in more rounded cells and matured extracellular matrix. Stromal cell-derived factor-1 (SDF-1) enhanced the migration of hMeSPCs, whereas AMD3100 abolished the chemotactic effects of SDF-1 on hMeSPCs, both in vitro and in vivo. In an experimental OA model, transplantation of hMeSPCs effectively protected articular cartilage, as evidenced by reduced expression of OA markers such as collagen I, collagen X, and hypoxia-inducible factor 2α but increased expression of collagen II. Our study demonstrated for the first time that intra-articular injection of hMeSPCs enhanced meniscus regeneration through the SDF-1/CXCR4 axis. Our study highlights a new strategy of intra-articular injection of hMeSPCs for meniscus regeneration.
半月板损伤在临床上较为常见。目前的手术治疗包括半月板部分或全部切除术,在短期内可缓解疼痛,但长期往往会导致骨关节炎(OA)。在这项研究中,我们报告了一种通过关节内注射新型人半月板干/祖细胞(hMeSPC)来保护关节软骨的新策略。我们发现 hMeSPC 具有间充质干细胞的特征,并且高表达 II 型胶原。在大鼠半月板损伤模型中,hMeSPC 移植不仅导致更多的新组织形成和更清晰的形状,而且还导致更圆的细胞和成熟的细胞外基质。基质细胞衍生因子-1(SDF-1)增强了 hMeSPC 的迁移,而 AMD3100 则在体外和体内消除了 SDF-1 对 hMeSPC 的趋化作用。在实验性 OA 模型中,hMeSPC 移植有效地保护了关节软骨,OA 标志物如 I 型胶原、X 型胶原和缺氧诱导因子 2α 的表达减少,而 II 型胶原的表达增加。我们的研究首次证明,关节内注射 hMeSPC 通过 SDF-1/CXCR4 轴增强了半月板的再生。我们的研究强调了一种通过关节内注射 hMeSPC 来促进半月板再生的新策略。