Circulation Research RES Comparative Efficacy of Intracoronary Allogeneic Mesenchymal Stem Cells and Cardiosphere-Derived Cells in Swine with Hibernating Myocardium MSCs vs. CDCs in Hibernating Myocardium CIRCRES/2015/306850 CIRCRES/2015/306850 10.1161/CIRCRESAHA.115.306850 117 09/11/15 7 Bridges-Lyman Gemma 410-3275005 410-3279322 Bolli, Roberto University of Louisville School of Medicine Dr. John M Canty canty@buffalo.edu Dr. The State University of New York at Buffalo UB Clinical and Translational Research Center, Suite 7030 875 Ellicott Street Buffalo New York 14203 UNITED STATES 716 829-2663 (716) 854-1840 24942 Brian R Weil The State University of New York at Buffalo bweil@buffalo.edu 157652 Gen Suzuki The State University of New York at Buffalo gsuzuki@buffalo.edu 75297 Merced M Leiker The State University of New York at Buffalo leiker@buffalo.edu 157653 James A Fallavollita The State University of New York at Buffalo jaf7@buffalo.edu 28904 John M Canty The State University of New York at Buffalo canty@buffalo.edu 24942 05/15/2015 05/15/2015 08/07/2015 08/12/2015 08/12/2015 Regular Article allogeneic cell therapy cell therapy <p><i><b><u>Rationale:</u></b></i> Allogeneic bone marrow-derived mesenchymal stem cells (MSCs) and cardiosphere-derived cells (CDCs) have each entered clinical trials but a direct comparison of these cell types has not been performed in a large animal model of hibernating myocardium. </p><p><i><b><u>Objective:</u></b></i> Using completely blinded methodology, compare the efficacy of global intracoronary allogeneic MSCs (icMSCs,~35x10⁶) and CDCs (icCDCs,~35x10⁶) vs. vehicle in cyclosporine-immunosuppressed swine with a chronic LAD stenosis (n=26). </p><p><i><b><u>Methods and Results:</u></b></i> Studies began 3-months after instrumentation when wall-thickening (%WT) was reduced (LAD%WT 38±11% (mean±SD) vs. 83±26% in remote, p<0.01) and similar among groups. Four-weeks after treatment, LAD%WT increased similarly following icCDCs and icMSCs, while it remained depressed in vehicle-treated controls (icMSCs: 51±13%; icCDCs: 51±17%; vehicle: 34±3%, treatments p<0.05 vs. vehicle). There was no change in myocardial perfusion. Both icMSCs and icCDCs increased LAD myocyte nuclear density (icMSCs: 1601±279 nuclei/mm2, icCDCs: 1569±294 nuclei/mm2, vehicle: 973±181 nuclei/mm2, treatments p<0.05 vs. vehicle) and reduced myocyte diameter (icMSCs: 16.4±1.5 µm, icCDCs: 16.8±1.2 µm, vehicle: 20.2±3.7 µm, treatments p<0.05 vs. vehicle) to the same extent. Similar changes in myocyte nuclear density and diameter were observed in the remote region of cell-treated animals. Cell fate analysis using Y-FISH demonstrated rare cells from sex-mismatched donors. </p><p><i><b><u>Conclusions:</u></b></i> Allogeneic icMSCs and icCDCs exhibit comparable therapeutic efficacy in a large animal model of hibernating myocardium. Both cell types produced equivalent increases in regional function and stimulated myocyte regeneration in ischemic and remote myocardium. The activation of endogenous myocyte proliferation and regression of myocyte cellular hypertrophy support a common mechanism of cardiac repair. </p> 0 0 0 7 7 no yes CircRes_CIRCRES-2015-306850.xml CircRes_CIRCRES-2015-306850_file1.docx CircRes_CIRCRES-2015-306850_supp1.pdf

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CircRes_CIRCRES-2015-306850_supp2.pdf CircRes_CIRCRES-2015-306850_merge.pdf CircRes_CIRCRES-2015-306850_Canty_24942_disclosure.pdf CircRes_CIRCRES-2015-306850_Canty_24942_copyright.pdf CircRes_CIRCRES-2015-306850_Suzuki_75297_disclosure.pdf CircRes_CIRCRES-2015-306850_Suzuki_75297_copyright.pdf CircRes_CIRCRES-2015-306850_Leiker_157653_disclosure.pdf CircRes_CIRCRES-2015-306850_Leiker_157653_copyright.pdf CircRes_CIRCRES-2015-306850_Fallavollita_28904_disclosure.pdf CircRes_CIRCRES-2015-306850_Fallavollita_28904_copyright.pdf CircRes_CIRCRES-2015-306850_Weil_157652_disclosure.pdf CircRes_CIRCRES-2015-306850_Weil_157652_copyright.pdf PAP: 08/13/15 Please note that the authors have agreed to pay $425 in excess page charges. Funding: Howard Hughes Medical Institute (HHMI): No National Institutes of Health (NIH): Yes Not applicable for this manuscript: No Other: Yes Wellcome Trust: No Subject Codes: [130] Animal models of human disease [7] Chronic ischemic heart disease [105] Contractile function gbridgeslyman