{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,31]],"date-time":"2025-12-31T18:19:21Z","timestamp":1767205161649,"version":"build-2238731810"},"reference-count":62,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Medical Research Council","award":["MR\/P026508\/1"],"award-info":[{"award-number":["MR\/P026508\/1"]}]},{"name":"Physiology society","award":["R\/102466"],"award-info":[{"award-number":["R\/102466"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Cells"],"abstract":"<jats:p>We have previously shown that skeletal muscle-derived Sca-1+\/PW1+\/Pax7\u2212 interstitial cells (PICs) are multi-potent and enhance endogenous repair and regeneration. Here, we investigated the regenerative potential of PICs following intramyocardial transplantation in mice subjected to an acute myocardial infarction (MI). MI was induced through the ligation of the left anterior descending coronary artery in 8-week old male C57BL\/6 mice. 5 \u00d7 105 eGFP-labelled PICs (MI + PICs; n = 7) or PBS (MI-PBS; n = 7) were injected intramyocardially into the border zone. Sham mice (n = 8) were not subjected to MI, or the transplantation of PICs or PBS. BrdU was administered via osmotic mini-pump for 14 days. Echocardiography was performed prior to surgery (baseline), and 1-, 3- and 6-weeks post-MI and PICs transplantation. Mice were sacrificed at 6 weeks post-MI + PICs transplantation, and heart sections were analysed for fibrosis, hypertrophy, engraftment, proliferation, and differentiation of PICs. A significant (p &lt; 0.05) improvement in ejection fraction (EF) and fractional shortening was observed in the MI-PICs group, compared to MI + PBS group at 6-weeks post MI + PICs transplantation. Infarct size\/fibrosis of the left ventricle significantly (p &lt; 0.05) decreased in the MI-PICs group (14.0 \u00b1 2.5%), compared to the MI-PBS group (32.8 \u00b1 2.2%). Cardiomyocyte hypertrophy in the border zone significantly (p &lt; 0.05) decreased in the MI-PICs group compared to the MI-PBS group (330.0 \u00b1 28.5 \u00b5M2 vs. 543.5 \u00b1 26.6 \u00b5m2), as did cardiomyocyte apoptosis (0.6 \u00b1 0.9% MI-PICs vs. 2.8 \u00b1 0.8% MI-PBS). The number of BrdU+ cardiomyocytes was significantly (p &lt; 0.05) increased in the infarct\/border zone of the MI-PICs group (7.0 \u00b1 3.3%), compared to the MI-PBS group (1.7 \u00b1 0.5%). The proliferation index (total BrdU+ cells) was significantly increased in the MI-PICs group compared to the MI-PBS group (27.0 \u00b1 3.4% vs. 7.6 \u00b1 1.0%). PICs expressed and secreted pro-survival and reparative growth factors, supporting a paracrine effect of PICs during recovery\/remodeling. Skeletal muscle-derived PICs show significant reparative potential, attenuating cardiac remodelling following transplantation into the infarcted myocardium. PICs can be easily sourced from skeletal muscle and therefore show promise as a potential cell candidate for supporting the reparative and regenerative effects of cell therapies.<\/jats:p>","DOI":"10.3390\/cells11244050","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T02:20:57Z","timestamp":1671070857000},"page":"4050","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Transplantation of Skeletal Muscle-Derived Sca-1+\/PW1+\/Pax7\u2212 Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9580-4746","authenticated-orcid":false,"given":"Prashant J","family":"Ruchaya","sequence":"first","affiliation":[{"name":"Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"},{"name":"Centre for Gene Therapy and Regenerative Medicine, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"},{"name":"School of Health, Sport and Biosciences, Stratford Campus, University of East London, London E16 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7273-639X","authenticated-orcid":false,"given":"Fiona C.","family":"Lewis-McDougall","sequence":"additional","affiliation":[{"name":"Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"},{"name":"Centre for Gene Therapy and Regenerative Medicine, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"},{"name":"The William Harvey Research Institute, Charterhouse Square, Barts & The London School of Medicine & Dentistry, Queen Mary University of London, London EC1M 6BQ, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nitiphat","family":"Sornkarn","sequence":"additional","affiliation":[{"name":"Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"},{"name":"Centre for Gene Therapy and Regenerative Medicine, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachin","family":"Amin","sequence":"additional","affiliation":[{"name":"Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"},{"name":"Centre for Gene Therapy and Regenerative Medicine, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin","family":"Grimsdell","sequence":"additional","affiliation":[{"name":"Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"},{"name":"Centre for Gene Therapy and Regenerative Medicine, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abeer","family":"Shaalan","sequence":"additional","affiliation":[{"name":"Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"},{"name":"Centre for Gene Therapy and Regenerative Medicine, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guilia","family":"Gritti","sequence":"additional","affiliation":[{"name":"Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"},{"name":"Centre for Gene Therapy and Regenerative Medicine, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyi Thar","family":"Soe","sequence":"additional","affiliation":[{"name":"School of Health, Sport and Biosciences, Stratford Campus, University of East London, London E16 2RD, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7574-2162","authenticated-orcid":false,"given":"James E.","family":"Clark","sequence":"additional","affiliation":[{"name":"Rayne Institute, School of Cardiovascular and Metabolic Medicine and Sciences, Faculty of Life Sciences & Medicine, King\u2019s College London, St Thomas\u2019 Campus, London SE1 7EH, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2733-3361","authenticated-orcid":false,"given":"Georgina M.","family":"Ellison-Hughes","sequence":"additional","affiliation":[{"name":"Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"},{"name":"Centre for Gene Therapy and Regenerative Medicine, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King\u2019s College London, Guy\u2019s Campus, London SE1 1UL, UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1002\/j.2040-4603.2015.tb00658.x","article-title":"Physiological Implications of Myocardial Scar Structure","volume":"5","author":"Richardson","year":"2015","journal-title":"Compr. 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