Elisa Avolio1, Marco Meloni1, Helen L Spencer1, Federica Riu1, Rajesh Katare1, Giuseppe Mangialardi1, Atsuhiko Oikawa1, Iker Rodriguez-Arabaolaza1, Zexu Dang1, Kathryn Mitchell1, Carlotta Reni1, Valeria V Alvino1, Jonathan Rowlinson1, Ugolini Livi1, Daniela Cesselli1, Gianni Angelini1, Costanza Emanueli1, Antonio P Beltrami1, Paolo Madeddu2. 1. From the Experimental Cardiovascular Medicine (E.A., H.L.S., F.R., R.K., G.M., A.O., I.R.-A., Z.D., K.M., C.R., V.V.A., J.R., P.M.) and Vascular Pathology and Regeneration (M.M., C.E.), School of Clinical Sciences, University of Bristol, Bristol, United Kingdom; Institute of Cardiovascular and Medical Sciences (M.M.), University of Glasgow, Glasgow, United Kingdom; Department of Physiology, University of Otago, Dunedin, New Zealand (R.K.); Department of Medical and Biological Sciences (D.C., A.P.B.) and Department of Experimental Medical and Clinical Sciences (U.L.), University of Udine, Udine, Italy; and Cardiac Surgery, Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom (G.A.). 2. From the Experimental Cardiovascular Medicine (E.A., H.L.S., F.R., R.K., G.M., A.O., I.R.-A., Z.D., K.M., C.R., V.V.A., J.R., P.M.) and Vascular Pathology and Regeneration (M.M., C.E.), School of Clinical Sciences, University of Bristol, Bristol, United Kingdom; Institute of Cardiovascular and Medical Sciences (M.M.), University of Glasgow, Glasgow, United Kingdom; Department of Physiology, University of Otago, Dunedin, New Zealand (R.K.); Department of Medical and Biological Sciences (D.C., A.P.B.) and Department of Experimental Medical and Clinical Sciences (U.L.), University of Udine, Udine, Italy; and Cardiac Surgery, Bristol Heart Institute, School of Clinical Sciences, University of Bristol, Bristol, United Kingdom (G.A.). Paolo.Madeddu@bristol.ac.uk.
Abstract
RATIONALE: Optimization of cell therapy for cardiac repair may require the association of different cell populations with complementary activities. OBJECTIVE: Compare the reparative potential of saphenous vein-derived pericytes (SVPs) with that of cardiac stem cells (CSCs) in a model of myocardial infarction, and investigate whether combined cell transplantation provides further improvements. METHODS AND RESULTS: SVPs and CSCs were isolated from vein leftovers of coronary artery bypass graft surgery and discarded atrial specimens of transplanted hearts, respectively. Single or dual cell therapy (300 000 cells of each type per heart) was tested in infarcted SCID (severe combined immunodeficiency)-Beige mice. SVPs and CSCs alone improved cardiac contractility as assessed by echocardiography at 14 days post myocardial infarction. The effect was maintained, although attenuated at 42 days. At histological level, SVPs and CSCs similarly inhibited infarct size and interstitial fibrosis, SVPs were superior in inducing angiogenesis and CSCs in promoting cardiomyocyte proliferation and recruitment of endogenous stem cells. The combination of cells additively reduced the infarct size and promoted vascular proliferation and arteriogenesis, but did not surpass single therapies with regard to contractility indexes. SVPs and CSCs secrete similar amounts of hepatocyte growth factor, vascular endothelial growth factor, fibroblast growth factor, stem cell factor, and stromal cell-derived factor-1, whereas SVPs release higher quantities of angiopoietins and microRNA-132. Coculture of the 2 cell populations results in competitive as well as enhancing paracrine activities. In particular, the release of stromal cell-derived factor-1 was synergistically augmented along with downregulation of stromal cell-derived factor-1-degrading enzyme dipeptidyl peptidase 4. CONCLUSIONS: Combinatory therapy with SVPs and CSCs may complementarily help the repair of infarcted hearts.
RATIONALE: Optimization of cell therapy for cardiac repair may require the association of different cell populations with complementary activities. OBJECTIVE: Compare the reparative potential of saphenous vein-derived pericytes (SVPs) with that of cardiac stem cells (CSCs) in a model of myocardial infarction, and investigate whether combined cell transplantation provides further improvements. METHODS AND RESULTS: SVPs and CSCs were isolated from vein leftovers of coronary artery bypass graft surgery and discarded atrial specimens of transplanted hearts, respectively. Single or dual cell therapy (300 000 cells of each type per heart) was tested in infarcted SCID (severe combined immunodeficiency)-Beige mice. SVPs and CSCs alone improved cardiac contractility as assessed by echocardiography at 14 days post myocardial infarction. The effect was maintained, although attenuated at 42 days. At histological level, SVPs and CSCs similarly inhibited infarct size and interstitial fibrosis, SVPs were superior in inducing angiogenesis and CSCs in promoting cardiomyocyte proliferation and recruitment of endogenous stem cells. The combination of cells additively reduced the infarct size and promoted vascular proliferation and arteriogenesis, but did not surpass single therapies with regard to contractility indexes. SVPs and CSCs secrete similar amounts of hepatocyte growth factor, vascular endothelial growth factor, fibroblast growth factor, stem cell factor, and stromal cell-derived factor-1, whereas SVPs release higher quantities of angiopoietins and microRNA-132. Coculture of the 2 cell populations results in competitive as well as enhancing paracrine activities. In particular, the release of stromal cell-derived factor-1 was synergistically augmented along with downregulation of stromal cell-derived factor-1-degrading enzyme dipeptidyl peptidase 4. CONCLUSIONS: Combinatory therapy with SVPs and CSCs may complementarily help the repair of infarcted hearts.
Authors: Vincenzo Grimaldi; Alberto Zullo; Francesco Donatelli; Francesco Paolo Mancini; Francesco Cacciatore; Claudio Napoli Journal: J Thorac Dis Date: 2018-07 Impact factor: 2.895
Authors: Konstantinos E Hatzistergos; Dieter Saur; Barbara Seidler; Wayne Balkan; Matthew Breton; Krystalenia Valasaki; Lauro M Takeuchi; Ana Marie Landin; Aisha Khan; Joshua M Hare Journal: Circ Res Date: 2016-08-01 Impact factor: 17.367
Authors: Joseph B Moore; Xian-Liang Tang; John Zhao; Annalara G Fischer; Wen-Jian Wu; Shizuka Uchida; Anna M Gumpert; Heather Stowers; Marcin Wysoczynski; Roberto Bolli Journal: Basic Res Cardiol Date: 2018-11-16 Impact factor: 17.165