Menasché Philippe
Department of Cardiovascular Surgery, Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, 20 rue Leblanc, 75015 Paris, France.
Circulation. 2009 May 26;119(20):2735-40. doi: 10.1161/CIRCULATIONAHA.108.812693.
So far, the major safety issue raised by the use of stem cells for cardiac repair has been the occurrence of ventricular arrhythmias, particularly after skeletal myoblast transplantation. Although one cannot refute a potential intrinsic arrhythmogenicity of stem cells, primarily related to their common lack of electromechanical integration into the recipient myocardium, it is also important to recognize that patients eligible for cell replacement therapy are prone to develop arrhythmias because of their underlying ischemic heart disease. Another confounding factor is the method used for the intramyocardial delivery of the cells, which can cause enough inflammatory tissue damage to further increase ventricular irritability on top of an already high baseline level. Thus any strategy designed to minimize the risk of stem cell-associated ventricular arrhythmias should take into account, besides the cell-specific ability to appropriately couple with host cardiomyocytes, the method of cell transfer and the nature of the myocardial environment targeted for cell engraftment. A more accurate characterization of the baseline risk of arrhythmias in these patients would thus be helpful for better assessing the respective contribution of the donor cells and the host myocardium to these complications. The risk-to-benefit ratio of stem cell therapy will finally have to be revisited in light of the fact that because this baseline risk is usually high, most of these patients will in any way be fitted with an implantable defibrillator.
到目前为止，使用干细胞进行心脏修复引发的主要安全问题是室性心律失常的发生，尤其是在骨骼肌成肌细胞移植后。尽管不能否认干细胞可能存在内在的致心律失常性，这主要与其普遍缺乏与受体心肌的机电整合有关，但同样重要的是要认识到，适合细胞替代治疗的患者由于其潜在的缺血性心脏病而容易发生心律失常。另一个混杂因素是细胞心肌内递送所使用的方法，这可能会导致足够的炎症性组织损伤，从而在已经很高的基线水平之上进一步增加心室的易激性。因此，任何旨在将干细胞相关室性心律失常风险降至最低的策略，除了要考虑细胞与宿主心肌细胞适当耦联的特定能力外，还应考虑细胞转移方法以及细胞植入所针对的心肌环境的性质。因此，更准确地描述这些患者心律失常的基线风险，将有助于更好地评估供体细胞和宿主心肌对这些并发症的各自贡献。鉴于这种基线风险通常很高，大多数这些患者无论如何都将配备植入式除颤器，最终将不得不重新审视干细胞治疗的风险效益比。
