Transplantation of Skeletal Muscle-Derived Sca-1<sup>+</sup>/PW1<sup>+</sup>/Pax7<sup>−</sup> Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction
We have previously shown that skeletal muscle-derived Sca-1<sup>+</sup>/PW1<sup>+</sup>/Pax7<sup>−</sup> interstitial cells (PICs) are multi-potent and enhance endogenous repair and regeneration. Here, we investigated the regenerative potential of PICs following i...
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MDPI AG
2022-12-01
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| Online Access: | https://www.mdpi.com/2073-4409/11/24/4050 |
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| author | Prashant J Ruchaya Fiona C. Lewis-McDougall Nitiphat Sornkarn Sachin Amin Benjamin Grimsdell Abeer Shaalan Guilia Gritti Kyi Thar Soe James E. Clark Georgina M. Ellison-Hughes |
| author_facet | Prashant J Ruchaya Fiona C. Lewis-McDougall Nitiphat Sornkarn Sachin Amin Benjamin Grimsdell Abeer Shaalan Guilia Gritti Kyi Thar Soe James E. Clark Georgina M. Ellison-Hughes |
| author_sort | Prashant J Ruchaya |
| collection | DOAJ |
| description | We have previously shown that skeletal muscle-derived Sca-1<sup>+</sup>/PW1<sup>+</sup>/Pax7<sup>−</sup> 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 × 10<sup>5</sup> 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 (<i>p</i> < 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 (<i>p</i> < 0.05) decreased in the MI-PICs group (14.0 ± 2.5%), compared to the MI-PBS group (32.8 ± 2.2%). Cardiomyocyte hypertrophy in the border zone significantly (<i>p</i> < 0.05) decreased in the MI-PICs group compared to the MI-PBS group (330.0 ± 28.5 µM<sup>2</sup> vs. 543.5 ± 26.6 µm<sup>2</sup>), as did cardiomyocyte apoptosis (0.6 ± 0.9% MI-PICs vs. 2.8 ± 0.8% MI-PBS). The number of BrdU+ cardiomyocytes was significantly (<i>p</i> < 0.05) increased in the infarct/border zone of the MI-PICs group (7.0 ± 3.3%), compared to the MI-PBS group (1.7 ± 0.5%). The proliferation index (total BrdU+ cells) was significantly increased in the MI-PICs group compared to the MI-PBS group (27.0 ± 3.4% vs. 7.6 ± 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. |
| first_indexed | 2024-03-09T17:12:22Z |
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| last_indexed | 2024-03-09T17:12:22Z |
| publishDate | 2022-12-01 |
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| series | Cells |
| spelling | doaj.art-65802af6bc8d4326a602c5681ba33dba2023-11-24T13:54:57ZengMDPI AGCells2073-44092022-12-011124405010.3390/cells11244050Transplantation of Skeletal Muscle-Derived Sca-1<sup>+</sup>/PW1<sup>+</sup>/Pax7<sup>−</sup> Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial InfarctionPrashant J Ruchaya0Fiona C. Lewis-McDougall1Nitiphat Sornkarn2Sachin Amin3Benjamin Grimsdell4Abeer Shaalan5Guilia Gritti6Kyi Thar Soe7James E. Clark8Georgina M. Ellison-Hughes9Centre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London, Guy’s Campus, London SE1 1UL, UKCentre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London, Guy’s Campus, London SE1 1UL, UKCentre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London, Guy’s Campus, London SE1 1UL, UKCentre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London, Guy’s Campus, London SE1 1UL, UKCentre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London, Guy’s Campus, London SE1 1UL, UKCentre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London, Guy’s Campus, London SE1 1UL, UKCentre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London, Guy’s Campus, London SE1 1UL, UKSchool of Health, Sport and Biosciences, Stratford Campus, University of East London, London E16 2RD, UKRayne Institute, School of Cardiovascular and Metabolic Medicine and Sciences, Faculty of Life Sciences & Medicine, King’s College London, St Thomas’ Campus, London SE1 7EH, UKCentre for Human and Applied Physiological Sciences, School of Basic and Medical Biosciences, Faculty of Life Sciences & Medicine, King’s College London, Guy’s Campus, London SE1 1UL, UKWe have previously shown that skeletal muscle-derived Sca-1<sup>+</sup>/PW1<sup>+</sup>/Pax7<sup>−</sup> 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 × 10<sup>5</sup> 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 (<i>p</i> < 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 (<i>p</i> < 0.05) decreased in the MI-PICs group (14.0 ± 2.5%), compared to the MI-PBS group (32.8 ± 2.2%). Cardiomyocyte hypertrophy in the border zone significantly (<i>p</i> < 0.05) decreased in the MI-PICs group compared to the MI-PBS group (330.0 ± 28.5 µM<sup>2</sup> vs. 543.5 ± 26.6 µm<sup>2</sup>), as did cardiomyocyte apoptosis (0.6 ± 0.9% MI-PICs vs. 2.8 ± 0.8% MI-PBS). The number of BrdU+ cardiomyocytes was significantly (<i>p</i> < 0.05) increased in the infarct/border zone of the MI-PICs group (7.0 ± 3.3%), compared to the MI-PBS group (1.7 ± 0.5%). The proliferation index (total BrdU+ cells) was significantly increased in the MI-PICs group compared to the MI-PBS group (27.0 ± 3.4% vs. 7.6 ± 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.https://www.mdpi.com/2073-4409/11/24/4050skeletal muscle PW1<sup>+</sup>/Pax7<sup>−</sup> interstitial cells (PICs)myocardial infarctioncardiac repair and regeneration |
| spellingShingle | Prashant J Ruchaya Fiona C. Lewis-McDougall Nitiphat Sornkarn Sachin Amin Benjamin Grimsdell Abeer Shaalan Guilia Gritti Kyi Thar Soe James E. Clark Georgina M. Ellison-Hughes Transplantation of Skeletal Muscle-Derived Sca-1<sup>+</sup>/PW1<sup>+</sup>/Pax7<sup>−</sup> Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction Cells skeletal muscle PW1<sup>+</sup>/Pax7<sup>−</sup> interstitial cells (PICs) myocardial infarction cardiac repair and regeneration |
| title | Transplantation of Skeletal Muscle-Derived Sca-1<sup>+</sup>/PW1<sup>+</sup>/Pax7<sup>−</sup> Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction |
| title_full | Transplantation of Skeletal Muscle-Derived Sca-1<sup>+</sup>/PW1<sup>+</sup>/Pax7<sup>−</sup> Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction |
| title_fullStr | Transplantation of Skeletal Muscle-Derived Sca-1<sup>+</sup>/PW1<sup>+</sup>/Pax7<sup>−</sup> Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction |
| title_full_unstemmed | Transplantation of Skeletal Muscle-Derived Sca-1<sup>+</sup>/PW1<sup>+</sup>/Pax7<sup>−</sup> Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction |
| title_short | Transplantation of Skeletal Muscle-Derived Sca-1<sup>+</sup>/PW1<sup>+</sup>/Pax7<sup>−</sup> Interstitial Cells (PICs) Improves Cardiac Function and Attenuates Remodeling in Mice Subjected to Myocardial Infarction |
| title_sort | transplantation of skeletal muscle derived sca 1 sup sup pw1 sup sup pax7 sup sup interstitial cells pics improves cardiac function and attenuates remodeling in mice subjected to myocardial infarction |
| topic | skeletal muscle PW1<sup>+</sup>/Pax7<sup>−</sup> interstitial cells (PICs) myocardial infarction cardiac repair and regeneration |
| url | https://www.mdpi.com/2073-4409/11/24/4050 |
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