Cell therapies are an up and coming technology in orthopedic medicine that has the potential to provide regenerative treatments for musculoskeletal disease. Despite numerous cell therapies showing preclinical success for common musculoskeletal indications of disc degeneration and osteoarthritis, there have been mixed results when testing these therapies in humans during clinical trials. A theory behind the mixed success of these cell therapies is that the harsh microenvironments of the disc and knee they are entering inhibit their anabolism and survival. Therefore, there is much ongoing research looking into how to improve the survival and anabolism of cell therapies within these musculoskeletal disease environments. This includes research into improving cell function under specific microenvironmental conditions known to exist in the intervertebral disc (IVD) and knee environment such as hypoxia, low-nutrient conditions, hyperosmolarity, acidity, and inflammation. This research also includes improving differentiation of cells into desired native cell phenotypes to better enhance their survival and anabolism in the knee and IVD. This review highlights the effects of specific musculoskeletal microenvironmental challenges on cell therapies and what research is being done to overcome these challenges.

中文翻译：

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在严酷的肌肉骨骼疾病环境中提高细胞疗法的存活率和合成代谢。

细胞疗法是骨科医学中的一项新兴技术，有可能为肌肉骨骼疾病提供再生治疗。尽管许多细胞疗法在治疗椎间盘退变和骨关节炎的常见肌肉骨骼适应症方面取得了临床前成功，但在临床试验期间在人体中测试这些疗法时，结果却喜忧参半。这些细胞疗法的成功背后的一个理论是，它们进入的椎间盘和膝盖的恶劣微环境抑制了它们的合成代谢和存活。因此，有许多正在进行的研究正在研究如何在这些肌肉骨骼疾病环境中提高细胞疗法的存活率和合成代谢。这包括在已知存在于椎间盘 (IVD) 和膝关节环境中的特定微环境条件下改善细胞功能的研究，例如缺氧、低营养条件、高渗透压、酸度和炎症。这项研究还包括改善细胞向所需天然细胞表型的分化，以更好地提高它们在膝关节和 IVD 中的存活率和合成代谢。本综述重点介绍了特定肌肉骨骼微环境挑战对细胞疗法的影响，以及正在开展哪些研究以克服这些挑战。这项研究还包括改善细胞向所需天然细胞表型的分化，以更好地提高它们在膝关节和 IVD 中的存活率和合成代谢。本综述重点介绍了特定肌肉骨骼微环境挑战对细胞疗法的影响，以及正在开展哪些研究以克服这些挑战。这项研究还包括改善细胞向所需天然细胞表型的分化，以更好地提高它们在膝关节和 IVD 中的存活率和合成代谢。本综述重点介绍了特定肌肉骨骼微环境挑战对细胞疗法的影响，以及正在开展哪些研究以克服这些挑战。