Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc.

Exhaustion of nucleus pulposus progenitor cells with ageing and degeneration of the intervertebral disc.
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DOI:
10.1038/ncomms2226
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发表时间:
2012
影响因子:
16.6
通讯作者:
--
中科院分区:
综合性期刊1区
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--
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尽管椎间盘疾病的发病率很高,但人们对椎间盘细胞的变化及其再生潜力与衰老和椎间盘退变的关系知之甚少。在这里,我们确定的祖细胞群体是Tie 2阳性(Tie 2+)和二唾液酸神经节苷脂2阳性(GD 2+),在髓核从小鼠和人类。这些细胞形成表达II型胶原和聚集蛋白聚糖的球状体集落。它们是克隆多能的,分化成间充质谱系,并在移植到非肥胖糖尿病/严重联合免疫缺陷小鼠时诱导髓核组织重组。患者组织中Tie 2+细胞的频率随着年龄和椎间盘退变而显著降低,表明其再生能力耗尽。然而,祖细胞(Tie 2 + GD 2+)可以在简单的培养条件下从其前体细胞(Tie 2 + GD 2-)诱导。此外,血管生成素-1,Tie 2的配体,是至关重要的髓核细胞的存活。我们的研究结果为再生治疗和新的诊断标准提供了见解。 背痛和坐骨神经痛通常是由椎间盘退变引起的。Sakai和他的同事从椎间盘中鉴定出髓核祖细胞的一个亚群,并表明这些祖细胞的丢失与衰老和椎间盘退变相关。
Despite the high prevalence of intervertebral disc disease, little is known about changes in intervertebral disc cells and their regenerative potential with ageing and intervertebral disc degeneration. Here we identify populations of progenitor cells that are Tie2 positive (Tie2+) and disialoganglioside 2 positive (GD2+), in the nucleus pulposus from mice and humans. These cells form spheroid colonies that express type II collagen and aggrecan. They are clonally multipotent and differentiated into mesenchymal lineages and induced reorganization of nucleus pulposus tissue when transplanted into non-obese diabetic/severe combined immunodeficient mice. The frequency of Tie2+ cells in tissues from patients decreases markedly with age and degeneration of the intervertebral disc, suggesting exhaustion of their capacity for regeneration. However, progenitor cells (Tie2+GD2+) can be induced from their precursor cells (Tie2+GD2−) under simple culture conditions. Moreover, angiopoietin-1, a ligand of Tie2, is crucial for the survival of nucleus pulposus cells. Our results offer insights for regenerative therapy and a new diagnostic standard. Back pain and sciatica are often caused by intervertebral disc degeneration. Sakai and colleagues identify a subset of nucleus pulposus progenitor cells from the intervertebral disc and show that loss of these progenitor cells correlates with ageing and intervertebral disc degeneration.
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