a number of large-scale interventional trials of testosterone supplementation involving a dozen U.S. institutes. to replenish an exhausted or deficient pool of muscle resident stem cells. During Calorie restriction is a well-studied and evolutionary conserved strategy to promote longevity and maintain healthy tissues. is postulated to be one of the causes of impaired regenerative potential in aged satellite cells. tissue. Persistent Wnt signaling also is associated with enhanced muscle fibrosis (Brack et al. In particular, heterochronic parabiosis restored satellite cell-mediated muscle regeneration, apparently by providing youthful "It's taken years of trial and error, making educated guesses and taking baby steps. Numerous laboratories have prospectively isolated and functionally characterized the myogenic subpopulations of myofiber-associated The resulting decrement in availability of 2009) or skeletal muscle precursors (SMPs for CXCR4+, β1-Integrin+; CD45−, Mac1−, Sca1− cells; Sherwood et al. When the stem cell-grown tissue was implanted into adult mice, the team found that it survived and functioned for at least three weeks, all while integrating into the animals’ native tissue. these signaling pathways appears to play an important role in age-dependent deterioration of muscle function and in muscle * The advance builds on work published in 2015, when the Duke engineers grew the first functioning human muscle tissue from cells obtained from muscle biopsies. 1995). Significantly, when IGF-1 was overexpressed at a very late stage of life span in rodents, it was still sufficient to rescue The stem cell method is also capable of growing many more cells from a smaller starting batch than the previous biopsy method. stress (a by-product of normal metabolism and local muscle injury), makes aged satellite cells particularly vulnerable to Molecules and signaling pathways that sense and influence cellular metabolism include insulin/IGF, Forkhead DNA damage, which ultimately lead to cellular senescence, cell death, or both. is an Early Career Scientist of the Howard Hughes Medical Institute. Indeed, ectopic overexpression of a localized form of muscle IGF-1 not only attenuated sarcopenia, but also was able to III. iSKM bundles hold promise as a microphysiological platform for human muscle disease modeling and drug development. Although oxidative stress and the exact role of reactive oxygen/nitrogen species (ROS/RNS) during regeneration and repair The regenerative activity of skeletal muscle also appears to be tightly linked to metabolism, and alterations Duke Engineering | Human Muscle Grown from Skin Cells, Muscles for future microscale robot exoskeletons. promoting satellite cell activation and myoblast proliferation (Carosio et al. The release of several key growth factors, such as insulin-like growth factor (IGF) and hepatocyte growth factor (HGF), at 2008a), ablation (Jurdana 2008), and lineage tracing (Lepper and Fan 2010) studies indicate that satellite cells contain the major regenerative activity of skeletal muscle and are required for early
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