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J Thorac Cardiovasc Surg 2006;131:1310-1313
© 2006 The American Association for Thoracic Surgery

Evolving Technology

Cell replacement therapy: The functional importance of myocardial architecture and intercellular gap-junction distribution

Department of Cardiothoracic Surgery and Medicine, Drexel University College of Medicine, Philadelphia, Pa

Received for publication February 7, 2006; revisions received February 22, 2006; accepted for publication February 24, 2006.

^_* Address for reprints: J. Yasha Kresh, PhD, FACC, FAHA, Department of Cardiothoracic Surgery, Drexel University College of Medicine, 245 North 15th St, Mail Stop 111, Philadelphia, PA 19102 (Email: jkresh@Drexelmed.edu).

The first 300 words of the full text of this article appear below.

	Introduction

 
Cellular cardiomyoplasty is emerging as a plausible therapeutic approach designed to promote cardiac muscle regeneration and neovascularization after myocardial infarction. Numerous experimental studies suggest that the mere transfer and implantation of adult stem and progenitor cells can have a measurable effect on cardiac tissue perfusion and contractile function. ^1,2 A likely explanation for the observed improvement in cardiac performance remains elusive and controversial. ³ Much remains unknown in muscle biology, but the cell-based therapy "translation train" has left the platform ahead of schedule, with unforeseen stops and an indefinite destination. ⁴

Indeed, we are living in interesting times (hopefully not a curse). The dogma that the heart is a postmitotic organ composed of terminally differentiated myocytes that are incapable of re-entering the cell cycle is undergoing intense scrutiny and attack. ^3,5 Anversa and Kajstura ³ were instrumental in providing the rationale (and argument) for proclaiming that cardiac regeneration is part of normal cell-turnover homeostasis. A number of clinically amenable approaches for transplanting adult stem cells into areas exhibiting muscle contractile deficit are currently undergoing trials. ^6-8 Autologous skeletal myoblasts were injected directly into the wall of the injured myocardium, resulting in improved cardiac function. The mechanism of action remains largely unknown because these cells do not transdifferentiate into cardiac myocytes ⁹ or functionally (electromechanically) integrate into the working muscle syncytium. This lack of communication with native cardiomyocytes is problematic and might be the basis and substrate for the observed lethal arrhythmias. ⁹ In addition, the level of intercellular coupling required for skeletal cells to excite their adjoining neighbors is by necessity exceedingly high because of the inherently short (2.5 ms) action potential duration.

For these reasons, pressure has been intense to use bone marrow–derived cells that have been reported to transdifferentiate into a variety of somatic cells. The study ¹ that is credited with legitimizing this approach showed that . . . [Full Text of this Article]

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