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This Article Full Text Full Text (PDF) All Versions of this Article: 296/4/H927    most recent 00931.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Lee, J. Articles by Terracciano, C. M. N. Search for Related Content PubMed PubMed Citation Articles by Lee, J. Articles by Terracciano, C. M. N.

Adult progenitor cell transplantation influences contractile performance and calcium handling of recipient cardiomyocytes

Heart Science Centre, National Heart and Lung Institute, Imperial College London, Harefield Hospital, London, United Kingdom

Submitted 26 August 2008 ; accepted in final form 28 January 2009

Adult progenitor cell transplantation has been proposed for the treatment of heart failure, but the mechanisms effecting functional improvements remain unknown. The aim of this study was to test the hypothesis that, in failing hearts treated with cell transplantation, the mechanical properties and excitation-contraction coupling of recipient cardiomyocytes are altered. Adult rats underwent coronary artery ligation, leading to myocardial infarction and chronic heart failure. After 3 wk, they received intramyocardial injections of either 10⁷ green fluorescence protein (GFP)-positive bone marrow mononuclear cells or 5 x 10⁶ GFP-positive skeletal myoblasts. Four weeks after injection, both cell types increased ejection fraction and reduced cardiomyocyte size. The contractility of isolated GFP-negative cardiomyocytes was monitored by sarcomere shortening assessment, Ca²⁺ handling by indo-1 and fluo-4 fluorescence, and electrophysiology by patch-clamping techniques. Injection of either bone marrow cells or skeletal myoblasts normalized the impaired contractile performance and the prolonged time to peak of the Ca²⁺ transient observed in failing cardiomyocytes. The smaller and slower L-type Ca²⁺ current observed in heart failure normalized after skeletal myoblast, but not bone marrow cell, transplantation. Measurement of Ca²⁺ sparks suggested a normalization of sarcoplasmic reticulum Ca²⁺ leak after skeletal myoblast transplantation. The increased Ca²⁺ wave frequency observed in failing myocytes was reduced by either bone marrow cells or skeletal myoblasts. In conclusion, the morphology, contractile performance, and excitation-contraction coupling of individual recipient cardiomyocytes are altered in failing hearts treated with adult progenitor cell transplantation.

heart failure; cell therapy; excitation-contraction coupling; cell electrophysiology; paracrine mechanims