Ann Thorac Surg 2004;78:1812-1813
© 2004 The Society of Thoracic Surgeons
New technology
INVITED COMMENTARY
Shafie Fazel, MD,
Denis Angoulvant, MD,
Richard D. Weisel, MD
Division of Cardiac Surgery, Toronto General Hospital, EN 14-215, 200 Elizabeth St, Toronto, Ontario M5G-2C4, Canada
Pompilio and colleagues report on the mobilization, harvesting, and purification of AC133+ cells followed by myocardial implantation at the time of coronary artery bypass grafting (CABG). Cell therapy offers the promise to regenerate the heart after a myocardial infarction. Skeletal myoblasts were the first cell type to be transplanted at the time of CABG into regions that could not be revascularized to assess safety and possible efficacy [1]. This phase I trial was well controlled.
Recent studies demonstrated that bone marrow cells [2, 3] contributed to cardiac restoration. The studies stimulated clinical trials that evaluated the use of bone marrow mononuclear and endothelial progenitor cell preparations to repair the injured myocardium [4–6]. Cardiac stem cells [7, 8] may also contribute to cardiac regeneration and may be tested in clinical trials. Restraint, however, should be employed and clinical trials should be well designed and adequately controlled to determine the safety and evaluate efficacy of cell transplantation. We recommend the following guidelines:
Cell therapy for ischemic cardiomyopathy should be reserved for patients who have at least one ischemic region that cannot be revascularized by conventional means. The viability of the region should be determined preoperatively, and patients who will likely improve with revascularization alone should be excluded. Fully informed consent must be obtained.
The conditions of cell procurement and the culture of freshly isolated or cultured cells should be extensively studied before clinical application. Phase I trials should be based on sufficient preclinical investigations to ensure safety and promise efficacy. Cell isolation and expansion should be performed according to good laboratory practices, the facilities should conform to regulatory requirements, and the details should be sufficiently documented to allow reproduction of the study.
Patient safety must be ensured. Arrhythmias are a major concern associated with the implantation of myoblasts. The prophylactic use of antiarrhythmic drugs, such as amiodarone, or the insertion of an implantable defibrillator according to the guidelines established in the Multicenter Automatic Defibrillator Implantation. Trial (MADIT) II trial should be strongly considered. Studies that do not ensure patient safety are unethical.
Phase I studies should be conducted in patients who might benefit from the procedure, and reasonable attempts should be made to detect treatment efficacy. Cell engraftment, perfusion, and regional or global function should be routinely evaluated in these trials.
In summary, cell transplantation may become routine during CABG for patients who cannot be adequately revascularized. Which cells to use, whether they are fresh, expanded in vitro, or gene-enhancement, are questions that should be answered in the near future. However, the excitement for this field should not result in the abandonment of scientific rigor.
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Acknowledgments
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The authors would like to acknowledge the support of the Heart and Stroke Foundation of Ontario.
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References
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- Menasche P, Hagege AA, Vilquin JT, et al. Autologous skeletal myoblast transplantation for severe postinfarction left ventricular dysfunction. J Am Coll Cardiol. 2003;41:1078–1083[Abstract/Free Full Text]
- Orlic D, Kajstura J, Chimenti S, et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci USA. 2001;98:10344–10349[Abstract/Free Full Text]
- Orlic D, Kajstura J, Chimenti S, et al. Transplanted adult bone marrow cells repair myocardial infarcts in mice. Ann NY Acad Sci. 2001;938:221–229[Medline]
- Tse HF, Kwong YL, Chan JK, et al. Angiogenesis in ischaemic myocardium by intramyocardial autologous bone marrow mononuclear cell implantation. Lancet. 2003;361:47–49[Medline]
- Stamm C, Westphal B, Kleine HD, et al. Autologous bone-marrow stem-cell transplantation for myocardial regeneration. Lancet. 2003;361:45–46[Medline]
- Assmus B, Schachinger V, Teupe C, et al. Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI). Circulation. 2002;106:3009–3017[Abstract/Free Full Text]
- Beltrami AP, Barlucchi L, Torella D, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114:763–776[Medline]
- Urbanek K, Quaini F, Tasca G, et al. Intense myocyte formation from cardiac stem cells in human cardiac hypertrophy. Proc Natl Acad Sci USA. 2003;100:10440–10445[Abstract/Free Full Text]
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