Bi Yanming, Ehirchiou Driss, Kilts Tina M, Inkson Colette A, Embree Mildred C, Sonoyama Wataru, Li Li, Leet Arabella I, Seo Byoung-Moo, Zhang Li, Shi Songtao, Young Marian F
Craniofacial and Skeletal Diseases Branch, National Institute of Dental and Craniofacial Research, US National Institutes of Health, 30 Convent Dr. 30/225 MSC 4320, Bethesda, Maryland 20892, USA.
Nat Med. 2007 Oct;13(10):1219-27. doi: 10.1038/nm1630. Epub 2007 Sep 9.
The repair of injured tendons remains a great challenge, largely owing to a lack of in-depth characterization of tendon cells and their precursors. We show that human and mouse tendons harbor a unique cell population, termed tendon stem/progenitor cells (TSPCs), that has universal stem cell characteristics such as clonogenicity, multipotency and self-renewal capacity. The isolated TSPCs could regenerate tendon-like tissues after extended expansion in vitro and transplantation in vivo. Moreover, we show that TSPCs reside within a unique niche predominantly comprised of an extracellular matrix, and we identify biglycan (Bgn) and fibromodulin (Fmod) as two critical components that organize this niche. Depletion of Bgn and Fmod affects the differentiation of TSPCs by modulating bone morphogenetic protein signaling and impairs tendon formation in vivo. Our results, while offering new insights into the biology of tendon cells, may assist in future strategies to treat tendon diseases.
受损肌腱的修复仍然是一个巨大的挑战，这主要是由于对肌腱细胞及其前体细胞缺乏深入的表征。我们发现人和小鼠的肌腱中存在一种独特的细胞群体，称为肌腱干/祖细胞（TSPCs），它具有克隆性、多能性和自我更新能力等普遍的干细胞特征。分离出的TSPCs在体外长期扩增和体内移植后能够再生出类似肌腱的组织。此外，我们发现TSPCs存在于一个主要由细胞外基质组成的独特生态位中，并且我们确定双糖链蛋白聚糖（Bgn）和纤调蛋白（Fmod）是构成这个生态位的两个关键成分。Bgn和Fmod的缺失通过调节骨形态发生蛋白信号影响TSPCs的分化，并损害体内肌腱的形成。我们的研究结果在为肌腱细胞生物学提供新见解的同时，可能有助于未来治疗肌腱疾病的策略。
