Affiliation:
1. Department of Biomedical Engineering University of Michigan Ann Arbor MI 48109 USA
2. BioInterfaces Institute University of Michigan Ann Arbor MI 48109 USA
3. Department of Materials Science & Engineering University of Michigan Ann Arbor MI 48109 USA
4. Program in Cellular and Molecular Biology University of Michigan Ann Arbor MI 48109 USA
Abstract
AbstractAdult stem cells occupy a niche that contributes to their function, but how stem cells rebuild their microenvironment after injury remains an open‐ended question. Herein, biomaterial‐based systems and metabolic labeling are utilized to evaluate how skeletal muscle stem cells deposit extracellular matrix. Muscle stem cells and committed myoblasts are observed to generate less nascent matrix than muscle resident fibro‐adipogenic progenitors. When cultured on substrates that matched the stiffness of physiological uninjured and injured muscles, muscle stem cells increased nascent matrix deposition with activation kinetics. Reducing the ability to deposit nascent matrix by an inhibitor of vesicle trafficking (Exo‐1) attenuated muscle stem cell function and mimicked impairments observed from muscle stem cells isolated from old muscles. Old muscle stem cells are observed to deposit less nascent matrix than young muscle stem cells, which is rescued with therapeutic supplementation of insulin‐like growth factors. These results highlight the role of nascent matrix production with muscle stem cell activation.
Funder
3M Foundation
National Science Foundation
Defense Advanced Research Projects Agency
U.S. Department of the Interior
Interior Business Center
Congressionally Directed Medical Research Programs
National Institute on Aging
Cited by
1 articles.
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