CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Karen L. Christman, PhD and
Randall J. Lee, MD, PhD*
* Cardiac Electrophysiology, MU East Tower, Box 1354, 500 Parnassus Avenue, San Francisco, CA 94143-1354 (Email: lee{at}medicine.ucsf.edu).
Our report (1) is the first study to demonstrate the beneficial effects of intramyocardial injection of a biopolymer alone in inducing angiogenesis and reducing infarct expansion. Furthermore, we have demonstrated that compositions of fibrin glue injected into ischemic myocardium prevent the negative remodeling associated with a myocardial infarction (MI) (2). These dramatic results were shown both for fibrin glue alone, and in material compositions of fibrin glue combined with transplanted, healthy myoblasts. Additionally, our report demonstrated that a fibrin glue scaffold increased the survival of contractile-type muscle cells, more specifically myoblasts, transplanted into myocardial tissue.
One hypothesis we tested was that an acellular intramyocardial injection of a biopolymer could prevent infarct expansion and prevent the continued worsening in left ventricular (LV) function following an MI. Dr. Chekanov and colleagues provide corroborative data regarding the utility of biopolymers. However, the emphasis of the experiments cited by Chekanov and colleagues had different objectives. In their earlier citations (3), Chekanov et al. used an autologous biologic glue containing fibrinogen epicardially to enhance the healing process of cardiomyoplasty. The autologous biologic glue was used "as an interlayer between the stimulated latissimus dorsi muscle and the myocardium to improve adhesion formation and cardiomyoplasty results."
Another hypothesis we tested was that fibrin glue matrix, in combination with myoblasts, enhances LV function. This test was specifically designed around use of a contractile type of cells. Accordingly, our work demonstrates an advancement by showing pronounced beneficial effects of fibrin glue-assisted myoblast transplantation into ischemic myocardium. Chekanov et al. (4) did report results of an experimental protocol to observe the effects of transplanting endothelial cells (ECs) in a fibrin matrix into ischemic myocardium. However, the experimental design was principally based upon a hypothesis of neovascularization and consisted of the following three groups: 1) ECs and fibrin matrix, 2) saline with denatured cells, and 3) a control group. The investigators did not include a fibrin matrix group alone or healthy ECs alone. Therefore, they did not test whether a biopolymer alone injected intramyocardially could produce angiogenesis or prevent the negative remodeling associated with an MI.
Additionally, without observing the effects of a healthy EC group without fibrin glue, the researchers could not determine the extent to which a fibrin matrix is beneficial in increasing cell transplantation and survival in the setting of myocardial injections. Still further, Chekanov and colleagues did not report any test protocols or observations regarding intramyocardial injections of fibrin glue in combination with contractile types of cells such as myoblasts.
The work done by Chekanov and colleagues is very interesting with respect to the objectives, experiences, observations, and results of their specific studies. Also, our work (1,2) does share some basic common features with the findings cited by Chekanov et al. However, the advances we made provide substantially new and different compositions of therapeutic materials, in vivo applications, and observations and results. Our work thus offers unique advancements and implications with respect to possible future applications to patient care. This is in particular the case with respect to demonstrating the benefits of injecting (a) acellular fibrin glue agents and (b) fibrin glue agents together with transplanted contractile-type cells (e.g., myoblasts) into ischemic myocardium.
Despite the distinct differences noted, we thank Dr. Chekanov and colleagues for sharing their experience with fibrin glue and to the advancement of the use of polymers as potential therapeutic agents.
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References
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1. Christman KL, Vardanian AJ, Sievers RE, Fang Q, Fok HH, Lee RJ. Injectable fibrin scaffold improves cell transplant survival, reduces infarct size, and induces neovasculature formation in ischemic myocardium J Am Coll Cardiol 2004;44:654-660.[Abstract/Free Full Text]
2. Christman KL, Fok HH, Sievers RE, Fang Q, Lee RJ. Injectable biopolymeric scaffold preserves cardiac function after myocardial infarction Tissue Eng 2004;10:403-409.[CrossRef][Web of Science][Medline]
3. Chekanov VS, Tchekanov GV, Rieder MA, et al. Biologic glue increases capillary ingrowth after cardiomyoplasty in an ischemic cardiomyopathy model ASAIO J 1996;42:M480-M487.[Web of Science][Medline]
4. Chekanov V, Akhtar M, Tchekanov GV, et al. Transplantation of autologous endothelial cell induces angiogenesis Pacing Clin Electrophysiol 2003;26:496-499.[CrossRef][Medline]
Related Article
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Cell Transplantation and Fibrin Matrix
- Valeri Chekanov, Nicholas Kipshidze, and Victor Nikolaychik
J. Am. Coll. Cardiol. 2005 45: 1734-1735.
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