Elucidating the function of a distinct cell population in adult mammalian tendons

Massachusetts General Hospital, Boston MA

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Abstract

Tendon injuries are common problems for active individuals and aging adults. Although surgical intervention can restore strength and mobility, frequent complications, such as a high failure rate and pain associated with movement, often occur. An improved understanding of the molecular and cellular mechanisms regulating tendon tissue maintenance, cell renewal, and injury response would have significant therapeutic implications. Studies have shown that cells from tendon tissues have stem/progenitor cell characteristics, and they are thought to contribute to tendon tissue homeostasis and repair. However, these studies were performed after extraction and expansion in culture, and our current knowledge as to the in vivo behaviors of these cells during maintenance and injury response is very limited. In addition, we have no means to prospectively identify, genetically target, and study unique tendon cell populations in their native environment. We propose to employ lineage tracing strategies to study cell turnover rates, gene expression, and functional properties of a uniquely genetically labeled tendon cell subset in vivo. Using these approaches, we will test the hypothesis that this specifically labeled subset of tendon cells are resident tendon progenitors and that a specific pathway is required for proper tendon healing responses. Knowledge of this distinct cell population will impact our fundamental understanding of the diversity of cell types within the tendon and would significantly advance our ability to directly isolate and genetically manipulate these cells. This work is a crucial step towards studying unique tendon progenitor cell populations in their native environment and will provide the foundation for future studies aimed at elucidating mechanisms regulating their activities.