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

阐明成年哺乳动物肌腱中独特细胞群的功能

基本信息

批准号：
9375253
负责人：
JENNA L GALLOWAY
金额：
$ 22.17万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2019-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9375253
关键词：
Acute Adult Affect Aging Alpha Cell Biological Assay Biology Biomechanics Cell Culture Techniques Cell Proliferation Cell Transplantation Cell physiology Cells Characteristics Cicatrix Clinical Environment Failure Flow Cytometry Foundations Future Gene Expression Genes Genetic Goals Health Care Costs Homeostasis Human Immunohistochemistry Individual Injury Knowledge Label Maintenance Modeling Molecular Movement Mus Operative Surgical Procedures Pain Pathway interactions Population Process Proliferating Property Regenerative response Research Role Site Stem cells Tendon Injuries Tendon structure Testing Therapeutic Tissues Transcription Coactivator Transgenes Transgenic Mice United States WNT Signaling Pathway Work achilles tendon age related base beta catenin cell behavior cell type experimental study healing improved in vivo injury and repair ligament injury novel progenitor prospective regenerative regenerative therapy repaired response response to injury scleraxis stem tendon development therapy development tissue degeneration

项目摘要

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.

肌腱损伤是活跃个体和老年人的常见问题。虽然手术