Migratory Chondrogenic Progenitor Cells from Repair Tissue during the Later Stages of Human Osteoarthritis

Migratory Chondrogenic Progenitor Cells from Repair Tissue during the Later Stages of Human Osteoarthritis
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DOI:
10.1016/j.stem.2009.01.015
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发表时间:
2009-04-03
期刊:
影响因子:
23.9
通讯作者:
Miosgel, Nicolai
Miosgel, Nicolai
中科院分区:
医学1区
文献类型:
--
作者:
Koelling, Sebastian;Kruegel, Jenny;Miosgel, Nicolai

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患病透明软骨的再生仍然是一个巨大的挑战,主要是因为无论是由重大损伤还是由年龄相关过程引起的退化都会过度扩展组织的自我更新能力。我们发现,在骨关节炎的晚期阶段,来自人类关节软骨的修复组织具有独特的祖细胞群,称为软骨形成祖细胞(CPC)。这些表现出干细胞的特性,如克隆形成,多能性和迁移活性。显示出高软骨形成潜力的分离的CPC显示出离体填充患病组织。此外,成骨转录因子runx-2的下调增强了软骨形成转录因子sox-9的表达。这反过来又增加了CPC的基质合成潜力,而不改变其迁移能力。我们的研究结果提供了新的见解祖细胞在患病软骨组织的背景下的生物学。我们的工作可能与骨关节炎后期新疗法的开发有关。
The regeneration of diseased hyaline cartilage continues to be a great challenge, mainly because degeneration-caused either by major injury or by age-related processes-can overextend the tissue's self-renewal capacity. We show that repair tissue from human articular cartilage during the late stages of osteoarthritis harbors a unique progenitor cell population, termed chondrogenic progenitor cells (CPCs). These exhibit stem cell characteristics such as clonogenicity, multipotency, and migratory activity. The isolated CPCs, which exhibit a high chondrogenic potential, were shown to populate diseased tissue ex vivo. Moreover, downregulation of the osteogenic transcription factor runx-2 enhanced the expression of the chondrogenic transcription factor sox-9. This, in turn, increased the matrix synthesis potential of the CPCs without altering their migratory capacity. Our results offer new insights into the biology of progenitor cells in the context of diseased cartilage tissue. Our work may be relevant in the development of novel therapeutics for the later stages of osteoarthritis.