{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T05:01:11Z","timestamp":1792645271330,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T00:00:00Z","timestamp":1678233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["5R35GM128594\u201004"],"award-info":[{"award-number":["5R35GM128594\u201004"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2023,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Over the past decade, advances in sepsis identification and management have resulted in decreased sepsis mortality. This increase in survivorship has highlighted a new clinical obstacle: chronic critical illness (CCI), for which there are no effective treatment options. Up to half of sepsis survivors suffer from CCI, which can include multi\u2010organ dysfunction, chronic inflammation, muscle wasting, physical and mental disabilities, and enhanced frailty. These symptoms prevent survivors from returning to regular day\u2010to\u2010day activities and are directly associated with poor quality of life.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Mice were subjected to cecal ligation and puncture (CLP) with daily chronic stress (DCS) as an <jats:italic>in vivo<\/jats:italic> model to study sepsis late\u2010effects\/sequelae on skeletal muscle components. Longitudinal monitoring was performed via magnetic resonance imaging, skeletal muscle and\/or muscle stem cell (MuSCs) assays (e.g., post\u2010necropsy wet muscle weights, minimum Feret diameter measurements, <jats:italic>in vitro<\/jats:italic> MuSC proliferation and differentiation, number of regenerating myofibres and numbers of Pax7\u2010positive nuclei per myofibre), post\u2010sepsis whole muscle metabolomics and MuSC isolation and high\u2010content transcriptional profiling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We report several findings supporting the hypothesis that MuSCs\/muscle regeneration are critically involved in post\u2010sepsis muscle recovery. First, we show that genetic ablation of muscle stem cells (MuSCs) impairs post\u2010sepsis muscle recovery (maintenance of 5\u20138% average lean mass loss compared with controls). Second, we observe impaired MuSCs expansion capacity and morphological defects at 26\u00a0days post\u2010sepsis compared with control MuSCs (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001). Third, when subjected to an experimental muscle injury, sepsis\u2010recovered mice exhibited evidence of impaired muscle regeneration compared with non\u2010septic mice receiving the same muscle injury (CLP\/DCS injured mean minimum Feret is 92.1% of control injured, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01). Fourth, we performed a longitudinal RNA sequencing study on MuSCs isolated from post\u2010sepsis mice and found clear transcriptional differences in all post\u2010sepsis samples compared with controls. At Day 28, CLP\/DCS mice satellite cells have multiple altered metabolic pathways, such as oxidative phosphorylation, mitochondrial dysfunction, sirtuin signalling and oestrogen receptor signalling, compared with controls (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our data show that MuSCs and muscle regeneration are required for effective post\u2010sepsis muscle recovery and that sepsis triggers morphological, functional, and transcriptional changes in MuSCs. Moving forward, we strive to leverage a more complete understanding of post\u2010sepsis MuSC\/regenerative defects to identify and test novel therapies that promote muscle recovery and improve quality of life in sepsis survivors.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13214","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T12:40:07Z","timestamp":1678279207000},"page":"1424-1440","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Muscle stem cells contribute to long\u2010term tissue repletion following surgical sepsis"],"prefix":"10.1002","volume":"14","author":[{"given":"Rebecca E.","family":"Schmitt","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Mayo Clinic  Rochester MN USA"},{"name":"Department of Anatomy, Cell Biology, and Physiology Indiana University School of Medicine  Indianapolis IN USA"},{"name":"Indiana Center for Musculoskeletal Health  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aneesha","family":"Dasgupta","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Mayo Clinic  Rochester MN USA"},{"name":"Department of Anatomy, Cell Biology, and Physiology Indiana University School of Medicine  Indianapolis IN USA"},{"name":"Indiana Center for Musculoskeletal Health  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paige C.","family":"Arneson\u2010Wissink","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srijani","family":"Datta","sequence":"additional","affiliation":[{"name":"Eden Prairie High School  Eden Prairie MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra M.","family":"Ducharme","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Mayo Clinic  Rochester MN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6830-708X","authenticated-orcid":false,"given":"Jason D.","family":"Doles","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology Mayo Clinic  Rochester MN USA"},{"name":"Department of Anatomy, Cell Biology, and Physiology Indiana University School of Medicine  Indianapolis IN USA"},{"name":"Indiana Center for Musculoskeletal Health  Indianapolis IN USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,3,8]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2016.0287"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(19)32989-7"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.01511"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/TA.0b013e318256e000"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/CCM.0000000000002074"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glab080"},{"key":"e_1_2_8_8_1","article-title":"Persistent inflammatory, immunosuppressed, catabolic syndrome (PICS): a new phenotype of multiple organ failure","volume":"1","author":"Rosenthal MD","year":"2015","journal-title":"J Adv Nutr Hum 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