Schmidt M B, Chen E H, Lynch S E
Schmidt Technical Consulting, LLC, 7 Amberg Drive, Pomfret Center, CT 06259, USA.
Osteoarthritis Cartilage. 2006 May;14(5):403-12. doi: 10.1016/j.joca.2005.10.011. Epub 2006 Jan 18.
Growth factors may enhance current cartilage repair techniques via multiple mechanisms including recruitment of chondrogenic cells (chemotaxis), stimulation of chondrogenic cell proliferation (mitogenesis) and enhancement of cartilage matrix synthesis. Two growth factors that have been studied in cartilage repair are insulin-like growth factor (IGF) and platelet derived growth factor (PDGF). IGF plays a key role in cartilage homeostasis, balancing proteoglycan synthesis and breakdown. Incorporating IGF into a fibrin clot placed in an equine cartilage defect improved the quality and quantity of repair tissue and reduced synovial inflammation. PDGF is a potent mitogenic and chemotactic factor for all cells of mesenchymal origin, including chondrocytes and mesenchymal stem cells. Resting zone chondrocytes cultured with PDGF demonstrated increased cell proliferation and proteoglycan production, while maturation of these cells along the endochondral pathway was inhibited. Pretreating chondrocytes with PDGF promotes heterotopic cartilage formation in the absence of any mechanical stimulus. PDGF has also been shown to be a potent stimulator of meniscal cell proliferation and migration. These studies and others suggest a potential role for these potent biological regulators of chondrocytes in cartilage repair. More work needs to be performed to define their appropriate dosing and the optimum delivery method. Combining tissue growth factors with a biological matrix can provide a physical scaffold for cell adhesion and growth as well as a means to control the release of these potent molecules. This could result in biological devices that enhance the predictability and quality of current cartilage repair techniques.
生长因子可通过多种机制增强当前的软骨修复技术,这些机制包括募集软骨形成细胞(趋化作用)、刺激软骨形成细胞增殖(有丝分裂原作用)以及增强软骨基质合成。在软骨修复中已被研究的两种生长因子是胰岛素样生长因子(IGF)和血小板衍生生长因子(PDGF)。IGF在软骨内环境稳定中起关键作用,平衡蛋白聚糖的合成与分解。将IGF掺入置于马软骨缺损处的纤维蛋白凝块中,可改善修复组织的质量和数量,并减轻滑膜炎症。PDGF是一种对所有间充质来源的细胞(包括软骨细胞和间充质干细胞)具有强大促有丝分裂和趋化作用的因子。用PDGF培养静止区软骨细胞,可显示细胞增殖增加和蛋白聚糖产生增多,而这些细胞沿软骨内成骨途径的成熟受到抑制。在没有任何机械刺激的情况下,用PDGF预处理软骨细胞可促进异位软骨形成。PDGF还被证明是半月板细胞增殖和迁移的强大刺激因子。这些研究及其他研究表明,这些强大的软骨细胞生物调节因子在软骨修复中具有潜在作用。需要开展更多工作来确定其合适的剂量和最佳递送方法。将组织生长因子与生物基质相结合,可为细胞黏附和生长提供物理支架,同时也是控制这些强大分子释放的一种手段。这可能会产生增强当前软骨修复技术可预测性和质量的生物装置。