CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Douwe E. Atsma, MD, PhD*,
Saskia L.M.A. Beeres, MD and
Martin J. Schalij, MD, PhD
* Department of Cardiology, C5-P, Leiden University Medical Center, P. O. Box 9600, 2300RC Leiden, the Netherlands (Email: d.e.atsma{at}lumc.nl).
We thank Dr. van Veen and colleagues for emphasizing the importance of optimal electrical coupling between cells transplanted into ischemically damaged myocardium and host cardiomyocytes. We fully agree that electrical integration of transplanted cells into the acceptor myocardium is essential to: 1) prevent occurrence of life-threatening arrhythmias; and 2) enhance the contractile capacity through coordinated contraction of host cardiomyocytes and transplanted cells.
Our recent in vitro model study, aimed at investigating the electrophysiological properties of human mesenchymal stem cells (MSCs), demonstrated connexin-mediated conduction of the action potential across MSCs (1). In our opinion, the observed impulse transmission (although mainly passive within the first 24 to 48 h) may be sufficient to prevent the occurrence of pro-arrhythmogenic large excitable gaps in transplanted areas. This is corroborated by the finding that at present no increased inducibility of arrhythmias was reported after transplantation of autologous bone-marrow–derived cells in patients with ischemic heart disease (2). In particular, repetitive electrocardiographic monitoring after MSC transplantation for acute myocardial infarction did not reveal increased occurrence of arrhythmias (3). Long-term in vitro recordings should elucidate whether conduction velocity, amplitude, and depolarization rate of the MSC electrograms increase >48 h after MSC application.
van Veen and colleagues suggest that transplantation of MSCs may not support the contractile capacity as MSCs injected in a rat myocardial infarction model lacked a well-developed functional contractile apparatus (4). However, a number of clinical studies have reported on improved left ventricular ejection fraction after bone marrow cell transplantation (2,3). Furthermore, it should be emphasized that the mechanism by which bone-marrow–cell transplantation improves cardiac function remains uncertain. The MSC-induced improvement in left ventricular ejection fraction described by Chen et al. (3) may either result from 1) differentiation of MSCs into cardiomyocytes (which inherently support myocardial contractility) or from 2) paracrine signaling by transplanted MSCs (which humorally stimulate the function of resident or recruited cardiac [progenitor] cells) (5). Clearly, additional research is warranted to provide more insight into the mechanism of the contractile improvement after bone-marrow–cell transplantation.
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1. Beeres SLMA, Atsma DE, van der Laarse A, et al. Human adult bone marrow mesenchymal stem cells repair experimental conduction block in rat cardiomyocyte cultures J Am Coll Cardiol 2005;46:1943-1952.[Abstract/Free Full Text]2. Wollert KC, Meyer GP, Lotz J, et al. Intracoronary autologous bone-marrow cell transfer after myocardial infarctionthe BOOST randomised controlled clinical trial. Lancet 2004;364:141-148.[CrossRef][Web of Science][Medline] 3. Chen SL, Fang WW, Ye F, et al. Effect on left ventricular function of intracoronary transplantation of autologous bone marrow mesenchymal stem cell in patients with acute myocardial infarction Am J Cardiol 2004;94:92-95.[CrossRef][Web of Science][Medline] 4. Dai W, Hale SL, Martin BJ, et al. Allogeneic mesenchymal stem cell transplantation in postinfarcted rat myocardiumshort- and long-term effects. Circulation 2005;112:214-223.[Abstract/Free Full Text] 5. Dawn B, Bolli R. Cardiac progenitor cells. The revolution continues Circ Res 2005;97:1080-1082.[Free Full Text]
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