间充质干细胞用于椎间盘修复的前景

J. Melrose
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引用次数: 2

摘要

椎间盘退变(DD)是影响全球80%人口的主要肌肉骨骼疾病[1]。相关的腰痛(LBP)在[2]中有重要的社会经济影响。在过去的25年里,人们研究了许多有前景的生物疗法来治疗退行性椎间盘病(DDD),并确定了许多潜在的生物干预分子靶点[3-5]。这些药物包括诱导细胞增殖、基质生成、调节基质金属蛋白酶(MMP)和金属蛋白酶组织抑制剂(TIMP)生成、炎症、血管长入和细胞活力[6]。IVD中的细胞密度很低[7],椎间盘细胞暴露在低氧张力、高乳酸水平、低营养和高静水压力的恶劣环境中,导致细胞死亡,细胞数量随着时间的推移而减少,原因是细胞衰老[8,9]、细胞凋亡[10,11]和自噬[12,13]。由此导致的DD细胞数量下降对任何治疗措施都提出了严峻的要求,以减轻这种情况。
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The promise of mesenchymal stem cells for intervertebral disc repair
Disc degeneration (DD) is a major musculoskeletal condition affecting 80% of the general global population [1]. The associated low back pain (LBP) has major socioeconomic impact reviewed in [2]. In the past 25 years a number of promising biological therapies have been investigated for the treatment of degenerative Disc Disease (DDD) and these have identified many potential molecular targets for biologic intervention [3-5]. These include agents which induce cellular proliferation, matrix production, regulate matrix metallo protease (MMP) and tissue inhibitor of metallo protease (TIMP) production, inflammation, vascular ingrowth and cell viability [6]. The cell density in the IVD is low [7] and disc cells are exposed to a hostile environment of low oxygen tension, high lactic acid levels, low nutrition and a high hydrostatic pressure leading to cell death and a diminution in cell numbers over time due to cellular senescence [8,9], apoptosis [10,11] and autophagy [12,13]. The resultant decline in cell number with DD places severe demands on any therapeutic measures to alleviate this condition.
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