Autologous Cardiomyotissue Implantation Promotes Myocardial Regeneration, Decreases Infarct Size, and Improves Left Ventricular Function

Abstract

Background-Cell therapy for myocardial infarction (MI) may be limited by poor cell survival and lack of transdifferentiation. We report a novel technique of implanting whole autologous myocardial tissue from preserved myocardial regions into infarcted regions. Methods and Results-Fourteen rats were used to optimize cardiomyotissue size with peritoneal wall implantation (300 m identified as optimal size). Thirty-nine pigs were used to investigate cardiomyotissue implantation in MI induced by left anterior descending balloon occlusion (10 animals died; male-to-female transplantation for tracking with in situ hybridization for Y chromosome, nϭ4 [2 donors and 2 MI animals]; acute MI implantation cohort at 1 hour, nϭ13; and healed MI implantation at 2 weeks, nϭ12 Key Words: myocardial infarction Ⅲ remodeling Ⅲ stem cells M yocardial infarction (MI) and its resultant left ventricular (LV) dysfunction remain a leading cause of mortality and morbidity. Different therapies for myocardial regeneration have been investigated with varying results and no definitive beneficial effects. [1][2][3][4][5][6][7][8][9][10][11] Concomitantly, the intrinsic regenerative potential of the myocardium has been increasingly recognized. [12][13][14] Adult cardiac stem cells injected into vasculature of rats after MI are able to differentiate into cardiomyocytes and arterioles. 15,16 In addition, it has been increasingly recognized that the delivery modality is a key limiting step in attempts at myocardial regeneration and angiogenesis with poor survival of transplanted cells (possible related to "milieu") and limited deposition and retention of injected cytokines. [17][18][19][20] This, coupled with mounting evidence relative to the lack of transdifferentiation potential of adult non-cardiac-derived stem cells, warrants a novel approach to myocardial regeneration. 21,22 Clinical Perspective on p 69We have developed a novel approach to adult cardiomyocyte transplantation. In a porcine model of MI, core biopsies of myocardial tissue are obtained from the preserved basal ventricular septum and used for implantation into the myocardial scar Received January 28, 2006; accepted October 8, 2010 MethodsAll experiments were performed in accordance with National Institutes of Health guidelines and were approved by the Institutional Animal Care and Use Committee at Beth Israel Deaconess Medical Center. Myotissue Sizing ExperimentsFourteen inbred rats (50 to 60 g) were used. Donor rats (nϭ3) were euthanized with CO 2 inhalation, and the heart was excised and placed in normal saline. Strips of varying diameters (100 to 500 mol/L) were obtained under a dissecting microscope. Eleven rats were then anesthetized with intraperitoneal ketamine/xylaxine (0.1 mL /100 g). The abdominal skin was incised and rectus muscle was exposed. Strips were implanted, and rectus fascia was closed with 10 -0 Prolene suture. Animals were divided into 5 groups (nϭ2 per group) with implantation of 100-, 200-, 300-, 400-, and 500-m strips (1 strip per animal). The animals were ...

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