基于干细胞的关节软骨修复与再生

H. J. Paek, Courtney Kim, R. Tuan
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引用次数: 2

摘要

关节软骨是一种高度特化的组织,当受到严重损伤时,其再生能力极其有限。因此,目前尚无临床可接受的无风险、无复发的治疗方案。治疗不当的破坏性和退行性软骨损伤通常会发展为进行性关节退行性变或骨关节炎。传统的手术治疗往往产生纤维软骨,不能支持原有的软骨功能,迅速恶化,而其他保守治疗只能起到缓解症状的作用。在这里,我们回顾了目前用于软骨修复的组织工程技术,并描述了我们为开发先进的基于细胞的工程结构来替代结构和生物功能,并促进新软骨的再生所做的努力。为了克服可获得的自体软骨细胞来源有限,只能提供有限的细胞群用于生长和修复,因此成体骨髓间充质干细胞(MSCs)的应用已被积极研究。生物相容性和可生物降解支架,包括聚ε-己内酯、聚l -乳酸、海藻酸盐和I型胶原,也被评估为其物理可操作性、相容性和间充质干细胞整合到宿主软骨组织的结构支持。MSCs与生物材料支架的结合产生了透明的软骨样组织,关节表面光滑,生化成分与天然软骨最相似,力学性能更强。由于骨髓来源的间充质干细胞通常是通过相当侵入性的方法提取的,最近的研究表明,脂肪来源的基质细胞可以通过侵入性较小的分离方法提供类似的治疗效果。基于越来越多的证据,未来的策略应该明确间充质干细胞的作用,并可能考虑将脂肪来源的间充质干细胞与耐用且生理上兼容的生物支架结合使用。
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Stem cell-based repair and regeneration of articular cartilage
Articular cartilage is a highly specialized tissue, that when critically injured has an extremely limited capacity for regeneration. Accordingly, a clinically acceptable treatment option without risks and recurrence is currently unavailable. Inadequately treated destructive and degenerative cartilage injuries will often develop into progressive joint degeneration or osteoarthritis. Conventional surgical treatments frequently produce fibrocartilage, which cannot support the original cartilage function and deteriorates rapidly, while other conservative therapies only offer symptomatic relief. Here, we review the current tissue engineering technology for cartilage repair and describe our efforts to develop advanced cell-based engineered constructs to replace structural and biological functions, and to facilitate the regeneration of new cartilage. To overcome the limited source of available autologous chondrocytes provide only a limited population for growth and repair, hence the utility of adult bone marrow derived mesenchymal stem cells (MSCs) have been actively investigated. Biocompatible and biodegradable scaffolds, including poly-ε-caprolactone, poly-L-lactic acid, alginate, and collagen type I, have also been evaluated for their physical maneuverability, compatibility, and structural support of mesenchymal stem cells integrated into host cartilage tissue. The combination of MSCs with biomaterial scaffolds produced hyaline cartilage-like tissue with smooth articular surfaces, biochemical compositions most like that of native cartilage, and with stronger mechanical properties. As bone marrow derived MSCs are typically extracted by rather invasive means, recent studies suggest that adipose-derived stromal cells may provide similar therapeutic benefits with isolation methods that are less invasive. Based on a growing body of evidence, future strategies should clarify the role of MSCs and perhaps consider the use of adipose-derived MSCs combined with a durable and physiologically compatible biological scaffold.
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