Article abstract
Nature Medicine 13, 1219 - 1227 (2007)
Published online: 9 September 2007 | doi:10.1038/nm1630
Identification of tendon stem/progenitor cells and the role of the extracellular matrix in their niche
Yanming Bi1, Driss Ehirchiou2, Tina M Kilts1, Colette A Inkson1, Mildred C Embree1, Wataru Sonoyama1, Li Li1, Arabella I Leet3, Byoung-Moo Seo1, Li Zhang2, Songtao Shi1,4 & Marian F Young1
Abstract
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.
- 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.
- Center for Vascular and Inflammatory Diseases, Department of Physiology, University of Maryland School of Medicine, 800 W. Baltimore Street, Baltimore, Maryland 21201, USA.
- Division of Pediatric Orthopaedics, Johns Hopkins University, 601 N. Caroline Street, Baltimore, Maryland 21287, USA.
- Center for Craniofacial Molecular Biology, University of Southern California School of Dentistry, 2250 Alcazar Street, CSA 103, Los Angeles, California 90033, USA.
Correspondence to: Marian F Young1 e-mail: myoung@dir.nidcr.nih.gov
Correspondence to: Songtao Shi1,4 e-mail: songtaos@usc.edu
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