Development of an in vitro model to test the efficacy of novel therapies for IVD degeneration.
Development of an in vitro model to test the efficacy of novel therapies for IVD degeneration.
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DOI：
10.1002/term.180
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发表时间：
2009-08
影响因子：
3.3
通讯作者：
Hoyland JA
中科院分区：
文献类型：
--
作者：
Le Maitre CL;Fotheringham AP;Freemont AJ;Hoyland JA
下腰痛(LBP)是全球范围内导致残疾的主要原因，与椎间盘(IVD)退变有关。目前对椎间盘退变的发病机制有了更深入的了解，这导致了针对潜在的病理和再生策略的一些未来可能的治疗方法的发展。尽管到目前为止结果是有希望的，但在模拟活体人体椎间盘机械环境的环境中进行此类疗法的研究是有问题的。体外模型系统的开发可以在与人类脊柱相似的负载环境中保持IVD组织的代谢活性，这对于测试未来基于细胞和组织工程的IVD退变治疗的有效性至关重要。在这里，使用我们的新型加载装置，能够模拟人类脊柱内经历的加载环境，我们培养了髓核组织外植体，每天施加长达2周的静液加载方案，并研究了蛋白多糖保留、代谢活性和细胞表型。在与体内负载环境相关的负载环境下培养的IVD组织保持了代谢细胞活性、蛋白多糖含量和细胞表型。事实上，与未加载的对照组相比，加载培养的IVD组织的所有参数都得到了改善。这样的模型对于评估未来抑制IVD退化或刺激IVD再生的治疗方法的可行性和有效性的研究是非常有价值的，其中体内负荷环境可能是其成败的关键。
Low back pain (LBP) is a major cause of disability worldwide that has been linked to intervertebral disc (IVD) degeneration. An improved understanding of the pathogenesis of disc degeneration is now developing, which is leading to the development of a number of possible future therapies targeted at the underlying pathology and regeneration strategies. Although results thus far are promising, the investigation of such therapies in an environment that mimics the mechanical environment of the human disc in vivo is problematic. The development of an in vitro model system that can maintain metabolically active IVD tissue within a loading environment pertaining to that of the human spine is crucial for testing the efficacy of future cell-based and tissue-engineering therapies for IVD degeneration. Here, using our novel loading rig, capable of mimicking the loading environment experienced within the human spine, we have cultured nucleus pulposus tissue explants, applied a daily hydrostatic loading regime for up to 2 weeks and investigated proteoglycan retention, metabolic activity and cellular phenotype. IVD tissue cultured under a loading environment pertaining to the in vivo loading environment maintained metabolic cell activity, proteoglycan content and cellular phenotype. Indeed, all parameters were improved in IVD tissue cultured with load compared to unloaded controls. Such a model is invaluable for investigations assessing the feasibility and efficacy of future therapeutic approaches to inhibiting degeneration or stimulating regeneration of the IVD, where the in vivo loading environment may be crucial to their success or failure.
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影响因子：
4.9
作者：
Le Maitre, Christine L;Hoyland, Judith A;Freemont, Anthony J
通讯作者：
Freemont, Anthony J
影响因子：
3
作者：
Ariga, K;Yonenobu, K;Yoshikawa, H
通讯作者：
Yoshikawa, H
影响因子：
3
作者：
Handa, T;Ishihara, H;Obata, K
通讯作者：
Obata, K
影响因子：
3
作者：
Bibby, SRS;Jones, DA;Urban, JPG
通讯作者：
Urban, JPG
DOI：
10.1016/0304-4165(86)90306-5
发表时间：
1986-09-04
期刊：
BIOCHIMICA ET BIOPHYSICA ACTA
影响因子：
--
作者：
FARNDALE, RW;BUTTLE, DJ;BARRETT, AJ
通讯作者：
BARRETT, AJ