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      Clinical Trials in the Surgical Management of Congestive Heart Failure: Surgical Ventricular Restoration and Autologous Skeletal Myoblast and Stem Cell Cardiomyoplasty

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          Abstract

          Despite continued advances in medical and surgical approaches for patients with ischemic cardiomyopathy, congestive heart failure (CHF) remains a growing cause of morbidity and mortality. Historically, surgical options for end-stage CHF have been limited. However, there are several surgical therapies now under clinical investigation that appear promising in the effort to reverse or restore the remodeled left ventricle. This review will focus on early but current clinical studies examining surgical ventricular restoration and autologous skeletal myoblast and stem cell transplantation. Although these emerging therapeutic options remain in the early stages of study and development, they hold promise in providing options to those patients with end-stage CHF.

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          Most cited references 15

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          Mesenchymal stem cell implantation in a swine myocardial infarct model: engraftment and functional effects.

          A novel therapeutic option for the treatment of acute myocardial infarction involves the use of mesenchymal stem cells (MSCs). The purpose of this study was to investigate whether implantation of autologous MSCs results in sustained engraftment, myogenic differentiation, and improved cardiac function in a swine myocardial infarct model. MSCs were isolated and expanded from bone marrow aspirates of 14 domestic swine. A 60-minute left anterior descending artery occlusion was used to produce anterior wall infarction. Piezoelectric crystals were placed within the ischemic region for measurement of regional wall thickness and contractile function. Two weeks later animals autologous, Di-I-labeled MSCs (6 x 10(7)) were implanted into the infarct by direct injection. Hemodynamic and functional measurements were obtained weekly until the time of sacrifice. Immunohistochemistry was used to assess MSC engraftment and myogenic differentiation. Microscopic analysis showed robust engraftment of MSCs in all treated animals. Expression of muscle-specific proteins was seen as early as 2 weeks and could be identified in all animals at sacrifice. The degree of contractile dysfunction was significantly attenuated at 4 weeks in animals implanted with MSCs (5.4% +/- 2.2% versus -3.37% +/- 2.7% in control). In addition, the extent of wall thinning after myocardial infarction was markedly reduced in treated animals. Mesenchymal stem cells are capable of engraftment in host myocardium, demonstrate expression of muscle specific proteins, and may attenuate contractile dysfunction and pathologic thinning in this model of left ventricular wall infarction. MSC cardiomyoplasty may have significant clinical potential in attenuating the pathology associated with myocardial infarction.
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            Regenerating functional myocardium: improved performance after skeletal myoblast transplantation.

            The adult heart lacks reserve cardiocytes and cannot regenerate. Therefore, a large acute myocardial infarction often develops into congestive heart failure. To attempt to prevent this progression, we transplanted skeletal myoblasts into cryoinfarcted myocardium of the same rabbits (autologous transfer), monitored cardiac function in vivo for two to six weeks and examined serial sections of the hearts by light and electron microscopy. Islands of different sizes comprising elongated, striated cells that retained characteristics of both skeletal and cardiac cells were found in the cryoinfarct. In rabbits in which myoblasts were incorporated, myocardial performance was improved. The ability to regenerate functioning muscle after autologous myoblast transplantation could have a important effect on patients after acute myocardial infarction.
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              In vivo magnetic resonance imaging of mesenchymal stem cells in myocardial infarction.

              We investigated the potential of magnetic resonance imaging (MRI) to track magnetically labeled mesenchymal stem cells (MR-MSCs) in a swine myocardial infarction (MI) model. Adult farm pigs (n=5) were subjected to closed-chest experimental MI. MR-MSCs (2.8 to 16x107 cells) were injected intramyocardially under x-ray fluoroscopy. MRIs were obtained on a 1.5T MR scanner to demonstrate the location of the MR-MSCs and were correlated with histology. Contrast-enhanced MRI demonstrated successful injection in the infarct and serial MSC tracking was demonstrated in two animals. MRI tracking of MSCs is feasible and represents a preferred method for studying the engraftment of MSCs in MI.
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                Author and article information

                Journal
                CRD
                Cardiology
                10.1159/issn.0008-6312
                Cardiology
                S. Karger AG
                978-3-8055-7739-7
                978-3-318-01077-0
                0008-6312
                1421-9751
                2004
                February 2004
                27 February 2004
                : 101
                : 1-3
                : 48-60
                Affiliations
                The Ohio State University Medical Center, Columbus, Ohio, USA
                Article
                75985 Cardiology 2004;101:48–60
                10.1159/000075985
                14988626
                © 2004 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                Page count
                Figures: 7, Tables: 2, References: 61, Pages: 13
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