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J Thorac Cardiovasc Surg 2003;125:1181-1182
© 2003 The American Association for Thoracic Surgery
Letters to the Editor |
National University of Singapore, Singapore
To the Editor:
We read with interest the article of Suzuki and colleagues,
1 "Single Fibers of Skeletal Muscle as a Novel Graft for Cell Transplantation to the Heart." They investigated the feasibility of single skeletal muscle fibers as a vehicle to deliver putative myoblasts-myotubes into the myocardium in rat models. They further demonstrated the improvement of cardiac function and histologic evidence of cell proliferation and survival after single muscle fiber engraftment into the infarcted myocardium.
This is an important study in skeletal myoblast transplantation for cardiac repair, because mechanisms for improvement of cardiac function after myoblast transplantation have not been clearly identified. Although clinical application of myoblast transplantation for cardiac repair is already being assessed in phase I human studies, 2 many questions regarding the optimization of the transplantation conditions and procedure remain unanswered. 3
It appears logical to consider that the number of myoblasts that repopulate the infarcted myocardium must be important. In all other experimental studies, a significantly larger number of cells were implanted. Improvement in myocardial function has been directly related to the number of cells injected which in rodents is 3 to 6 million cells and large animals as many as 1 billion cells. Suzuki and colleagues 1 in their study used only 4 single fibers per heart for injection. According to their findings, each single fiber retained 20 myoblasts, as assessed by immunostaining for M-cadherin, meaning that only 80 myoblasts were transplanted. Therefore myoblasts had to undergo extensive proliferation after transplantation to achieve an optimum cell count for beneficial effect. It seems unreasonable to expect that as few as 4 single skeletal fibers (80 myoblasts) would bring about significant improvement of heart function. From the figures shown, the extent of repopulation of the myocardium with cells is unclear, and only a few myotubules have been formed, which would be unlikely to improve cardiac function significantly in a severely damaged heart.
The disadvantages pointed out by Suzuki and colleagues 1 of using expanded cultures of myoblast as opposed to single fibers are only theoretic. The problem of embolism from myoblast injection has never been reported, even when they are injected intra-arterially or intracoronarily. 4,5 Similarly, in clinical perspective, delaying an elective operation on a patient in stable condition to expand the myoblast number is not a major problem. Our experience and the current literature do not indicate that repeated passaging of myoblasts leads to significant deterioration or problems.
One of the important findings in this article is the development of multinucleate branching myotubes. Because the grafted myofibers were postmitotic, it was deduced that skeletal myoblasts were the source of the newly formed fibers. In a porcine model of chronic ischemia with transient immunosuppression, we implanted lacZ-positive human myoblasts of greater than 95% purity. At 6 weeks we demonstrated similar formation of new branching centrally located multinucleate myotubules. Most of the nuclei stained positively for ß-galactosidase (Figure 1). We believe that after myoblast transplantation neomyogenesis results in fibers with phenotypic features similar to skeletal and cardiac muscles and that this is the mechanism of improvement in cardiac function.
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