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
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
Affiliations
Prashant J Ruchaya
Centre 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, UK
Fiona C. Lewis-McDougall
Centre 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, UK
Nitiphat Sornkarn
Centre 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, UK
Sachin Amin
Centre 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, UK
Benjamin Grimsdell
Centre 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, UK
Abeer Shaalan
Centre 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, UK
Guilia Gritti
Centre 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, UK
Kyi Thar Soe
School of Health, Sport and Biosciences, Stratford Campus, University of East London, London E16 2RD, UK
James E. Clark
Rayne Institute, School of Cardiovascular and Metabolic Medicine and Sciences, Faculty of Life Sciences & Medicine, King’s College London, St Thomas’ Campus, London SE1 7EH, UK
Georgina M. Ellison-Hughes
Centre 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, UK
We have previously shown that skeletal muscle-derived Sca-1+/PW1+/Pax7− 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 × 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 p p 2 vs. 543.5 ± 26.6 µm2), as did cardiomyocyte apoptosis (0.6 ± 0.9% MI-PICs vs. 2.8 ± 0.8% MI-PBS). The number of BrdU+ cardiomyocytes was significantly (p < 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.
