Richardson Stephen M, Hoyland Judith A, Mobasheri Reza, Csaki Constanze, Shakibaei Mehdi, Mobasheri Ali
Tissue Injury and Repair Group, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK.
J Cell Physiol. 2010 Jan;222(1):23-32. doi: 10.1002/jcp.21915.
Defects of load-bearing connective tissues such as articular cartilage and intervertebral disc (IVD) can result from trauma, degenerative, endocrine, or age-related disease. Current surgical and pharmacological options for the treatment of arthritic rheumatic conditions in the joints and spine are ineffective. Cell-based surgical therapies such as autologous chondrocyte transplantation (ACT) have been in clinical use for cartilage repair for over a decade but this approach has shown mixed results. This review focuses on the potential of mesenchymal stem cells (MSCs) as an alternative to cells derived from patient tissues in autologous transplantation and tissue engineering. Here we discuss the prospects of using MSCs in regenerative medicine and summarize the advantages and disadvantages of these cells in articular cartilage and IVD tissue engineering. We discuss the conceptual and practical difficulties associated with differentiating and pre-conditioning MSCs for subsequent survival in a physiologically harsh extracellular matrix, an environment that will be highly hypoxic, acidic, and nutrient deprived. Implanted MSCs will be exposed to traumatic physical loads and high levels of locally produced inflammatory mediators and catabolic cytokines. We also explore the potential of culture models of MSCs, fully differentiated cells and co-cultures as "proof of principle" ethically acceptable "3Rs" models for engineering articular cartilage and IVD in vitro for the purpose of replacing the use of animals in arthritis research.
承重结缔组织的缺陷，如关节软骨和椎间盘（IVD），可能由创伤、退行性病变、内分泌或与年龄相关的疾病引起。目前用于治疗关节和脊柱关节炎性风湿疾病的手术和药物治疗方法效果不佳。基于细胞的手术疗法，如自体软骨细胞移植（ACT），已在临床用于软骨修复十多年，但这种方法的效果参差不齐。本综述重点关注间充质干细胞（MSCs）在自体移植和组织工程中作为替代患者组织来源细胞的潜力。在此，我们讨论了在再生医学中使用MSCs的前景，并总结了这些细胞在关节软骨和IVD组织工程中的优缺点。我们讨论了在生理上恶劣的细胞外基质中分化和预处理MSCs以使其随后存活所涉及的概念和实际困难，这种环境将是高度缺氧、酸性和营养缺乏的。植入的MSCs将暴露于创伤性物理负荷以及高水平的局部产生的炎症介质和分解代谢细胞因子。我们还探讨了MSCs、完全分化细胞和共培养的培养模型作为“原理证明”的潜在可能性，这些模型是在体外工程化关节软骨和IVD的符合伦理的可接受的“3Rs”模型，目的是在关节炎研究中替代动物的使用。
