The main findings of our study question the efficacy of autologous cell transplantation for myocardial restoration in CABG surgery patients. This was proven by means of non-invasive bioimaging techniques which showed no evidence of clear improvement in tissue viability or function within akinetic and non-viable infarct regions.
The differentiation between viable myocardium and scar tissue has important clinical implications, because in patients with viable myocardium, revascularisation is likely to result in improvement of regional and global LV function, heart failure symptoms, and long-term prognosis [2, 3]. In contrast, regional LV dysfunction arising from transmural myocardial infarction with non-viable myocardium may be irreversible after revascularisation [4–6]. To treat this portion of the ischemic heart muscle a novel therapeutic strategy using bone marrow cells has been proposed as a potential alternative treatment for such patients, because these cells have been shown to improve structure and function in experimental myocardial infarction [11, 12]. Thereby, locally released paracrine factors may act by promoting angiogenesis .
Preliminary data in small patient numbers in whom bone marrow-derived cells have been injected into myocardial tissue suggest the safety and feasibility of cell transplantation. Hamano et al.  injected autologous mononuclear bone marrow cells directly into ungraftable myocardial territories during CABG surgery in 5 patients. Postoperative evaluation revealed no short-term toxicity or adverse events and the engrafted cells seemed to contribute to improved perfusion observed in these territories. In a similar study by Stamm et al. , injection of AC 133+ bone marrow cells in the peri-infarct zone in conjunction with CABG in 12 patients resulted in significantly improved global LV function as well as improved perfusion of the infarcted myocardium assessed by thallium scans. Tse et al.  found improvement in myocardial perfusion and segmental contractility as assessed by cardiac magnetic resonance imaging in ischemic myocardial segments of 8 patients treated with sole catheter-based intramyocardial implantation of autologous mononuclear bone marrow cells. Silva et al.  used transendocardial delivery of autologous bone marrow-derived mononuclear cells in heart transplant candidates with viable ischemic myocardium. After cell therapy exercise capacity improved, and 4 of the 5 patients were no longer eligible for cardiac transplantation. Most recently published studies  reported short-term functional improvement of transplantation of mononuclear bone marrow cells through an intracoronary delivery system in patients after successful percutaneous coronary intervention for acute ST-segment elevation myocardial infarct. In most of the studies the ischemic regions injected with cells were still viable and thus, despite the presence of clinically promising data, no conclusion can be drawn for the revitalising capacity of bone marrow cells.
In contrast, in our study injections were performed to non-viable myocardium. We did not find evidence that mononuclear bone marrow cells in combination with CABG are capable of restoring viability or function in patients with formerly non-viable infarcted myocardium. Transepicardial cell injection during open heart surgery into the core and border zone of infarct scar resulted in enhanced myocardial viability by 75% as determined by 99mTc-tetrofosmin SPECT and 18F-FDG-PET only in one patient. Though this finding is notable in that metabolically non-viable segments (99mTc-tetrofosmin SPECT and 18F-FDG uptake ≤50%) usually do not improve after revascularisation [4–6], the contribution of transplanted mononuclear bone marrow cells to resumed viability is unclear. In this study the median total injected mononuclear cell number as well as the median percentage and the range of CD34+, CD34+/CD133+ and CD34+/KDR+ cells were found to be in concordance with published data from other groups. Interestingly, the number of injected cells did not correlate with the change in myocardial viability.
We used 99mTc-tetrofosmin SPECT and 18F-FDG-PET as widely accepted reference standards for the non-invasive assessment of myocardial ischemia and viability [16, 17]. Different characteristics such as intact perfusion, cell membrane integrity, and preserved glucose metabolism form the basis for tissue characterisation by these different nuclear bioimaging modalities, that allow to distinguish transmural scar from dysfunctional but viable myocardial tissue [2, 4–8]. Thus, scintigraphic viability techniques using combined assessment of perfusion and metabolism offer an advantage over perfusion imaging alone, as for example used by Stamm et al. . However, overall we did not detect global LV function improvement at 3 months after cell transplantation and CABG surgery. From the preliminary data available no difference in regional LVEF before and after surgery could be demonstrated. However, differences in regional LVEF might be better evluated with cine magnetic resonance imaging (MRI) .
The major limitations of this ongoing study are the small numbers of patients and the absence of a control group as for most studies published so far. Importantly, all patients underwent cell implantation during bypass surgery. Therefore, an effect of improved myocardial blood flow due to surgical revascularisation itself on the viability as assessed by 99mTc-tetrofosmin SPECT and 18F-FDG-PET may be possible. Nevertheless, the preliminary findings reported here, focussing on myocardial viability with nuclear imaging techniques may contribute significantly to the field of stem cell therapy for the treatment of postinfarct patients, since the distinction between viable myocardium and irreversibly damaged scar tissue supplementary to clinical and angiographic data is of profound value. However, given the current incomplete knowledge on the mechanisms of transplanted adult stem cells in vivo, potential benefits and disadvantages must be considered in selecting candidate cells and patients for clinical trials. Clearly, there is a need for randomized, double-blind trials involving large numbers of patients before autologous bone marrow stem cells can be considered a clinically relevant option of therapy.