Intracoronary Transplantation Research Articles

Electrophysiological effects of intracoronary transplantation of autologous mesenchymal and endothelial progenitor cells

Autologous stem cell transplantation has been successfully used for repair of infarcted myocardium, but concerns have been raised regarding its pro-arrhythmic potential. This study aimed at using electrophysiological assessment, and the monitoring and data storage capacity of implanted cardioverter defibrillators (ICDs), in order to evaluate the possible proarrhythmic potential of stem cell transplantation. Five patients with a history of previous anteroseptal myocardial infarction and an implanted ICD for ventricular arrhythmias underwent intracoronary transplantation of autologous bone marrow-derived and culture-expanded mesenchymal stem cells in combination with endothelial progenitors. There was evidence of myocardial repair in three patients in whom segmental left ventricular wall motion improvement was detected on stress echocardiography. Before stem cell transplantation, clinical non-sustained ventricular tachycardia and inducible monomorphic ventricular tachycardia, or ventricular flutter at electrophysiology study were demonstrated in all patients. At 16-36 months follow-up, interrogation of the ICD failed to detect sustained or non-sustained ventricular arrhythmia in any patient. At repeat electrophysiology study, sustained ventricular arrhythmia was induced in two patients. Intracoronary transplantation of autologous mesenchymal and endothelial progenitor cells does not appear to be arrhythmogenic in humans. Further studies are needed on this important clinical issue.

Host Vascular Niche Contributes to Myocardial Repair Induced by Intracoronary Transplantation of Bone Marrow CD34+ Progenitor Cells in Infarcted Swine Heart

The effects of bone marrow cell transplantation (BMT) on myocardial infarct might be affected by host intrinsic circumferences. A best vascular niche was shown in the infarcted hearts with collateral vessels at 2 weeks after myocardial infarction (MI). BMT caused the greatest cardiac repairs after MI in the swine with better collateral vessels, which might be relative to richer collateral vessels, greater vessel densities, and higher expressions of basif fibroblast growth factor and stromal cell-derived factor-1 in the hearts before BMT. Our data suggest that existence of intrinsic collateral vessels contributes greatly to the beneficial effects of intracoronary BMT on cardiac repairs after MI. Disclosure of potential conflicts of interest is found at the end of this article.

Intracoronary Stem Cell Infusion in Heart Transplant Candidates

The stem cell transplantation is emerging as a potential therapeutic modality for patients with heart failure. It has been demonstrated that intracoronary stem cell transplantation had beneficial effects on left ventricular perfusion and contractile functions. We hypothesized that patients with end-stage ischemic cardiomyopathy, who are candidates for heart transplantation, could also benefit from autologous intracoronary stem cell transplantation. We performed a prospective, open-labeled study in 10 patients with end-stage ischemic cardiomyopathy, who were on the waiting list for heart transplantation. Each patient received bone marrow-derived mononuclear cell infusion via balloon catheter in the target vessel, which had been revascularized by percutaneous intervention and was patent before the procedure. Clinical and laboratory evaluations, a treadmill exercise test, echocardiography, and single photon emission tomography (SPECT) were performed to the patients at baseline and 6 months after stem cell infusion. At 6-month follow-up of the eight patients who were able to complete the study, we revealed a significant increase in ejection fraction (from 30.0 +/- 6.6% to 36.2 +/- 7.3%; p = 0.001) in echocardiographic evaluation. SPECT evaluation also displayed a reduction in infarct area (50.4 +/- 16.1% to 44.1 +/- 12.5%; p = 0.003). Both myocardial oxygen consumption (p = 0.001) and metabolic equivalents (p = 0.001) were significantly increased at 6-month follow-up. These results demonstrate that intracoronary stem cell transplantation ameliorates heart failure symptoms and improves left ventricular function and perfusion. Therefore intracoronary stem cell transplantation may be used as an alternative treatment option for heart transplant candidates.

Lack of Additional Benefit of Intracoronary Transplantation of Autologous Peripheral Blood Stem Cell in Patients With Acute Myocardial Infarction

Recently the potential of myocardial repair by transplantation of autologous bone marrow stem cells has been suggested. Whether the additional intracoronary transplantation of autologous peripheral blood stem cells (PBSC), which were mobilized by granulocyte-colony-stimulating factor (G-CSF), could safely improve myocardial function in patients with acute myocardial infarction (AMI) was investigated. Seventy-three patients with AMI who had successfully undergone percutaneous coronary intervention (PCI) were enrolled in the present prospective nonrandomized open-labeled study. Ten patients with elective PCI received G-CSF for 4 days followed by intracoronary PBSC transplantation. Thirty-two patients with primary PCI and 31 patients with recent AMI and elective PCI served as controls. The left ventricular (LV) function was evaluated using echocardiography and magnetic resonance imaging. G-CSF and intracoronary transplantation of PBSC did not incur any periprocedural myocardial damage. After 6 months, the LV ejection fraction was significantly improved in the cell therapy group. For 2 years of the follow-up period, there was no adverse clinical events, except one asymptomatic in-stent restenosis. However, comparable improvement of the LV ejection fraction was also identified in the primary PCI and elective PCI control groups. In the present study, additional intracoronary infusion of PBSC was safe and feasible for the patients with AMI who had undergone PCI, but did not lead to a significant improvement in LV function compared to standard reperfusion treatment.

Intracoronary Transplantation of Non-Expanded Peripheral Blood-Derived Mononuclear Cells Promotes Improvement of Cardiac Function in Patients With Acute Myocardial Infarction

Transplantation of non-expanded peripheral blood mononuclear cells (PBMNCs) enhances neovessel formation in ischemic myocardium and limbs by releasing angiogenic factors. This study was designed to examine whether intracoronary transplantation of PBMNCs improves cardiac function after acute myocardial infarction (AMI). After successful percutaneous coronary intervention (PCI) for a ST-elevation AMI with occlusion of proximal left anterior descending coronary artery within 24 h, patients received an intracoronary infusion of PBMNCs within 5 days after PCI (PBMNC group). PBMNCs were obtained from patients by COBE spectra-apheresis and concentrated to 10 ml, 3.3 ml of which was infused via over-the-wire catheter. The global left ventricular ejection fraction (LVEF) change from baseline to 6 months followup in th ePBMNC group that underwent standard PCI for similar AMI [corrected]. The primary endpoint was the global left ventricular ejection fraction (LVEF) change from baseline to 6 months' follow-up. The data showed that the absolute increase in LVEF was 7.4% in the control group and 13.4% (p=0.037 vs control) in the PBMNC group. Cell therapy resulted in a greater tendency of DeltaRegional ejection fraction (EF) or significant improvement in the wall motion score index and Tc-99m-tetrofosmin perfusion defect score associated with the infarct area, compared with controls. Moreover, intracoronary administration of PBMNCs did not exacerbate either left ventricular (LV) end-diastolic and end-systolic volume expansion or high-risk arrhythmia, without any adverse clinical events. Intracoronary infusion of non-expanded PBMNCs promotes improvement of LV systolic function. This less invasive and more feasible approach to collecting endothelial progenitor cells may provide a novel therapeutic option for improving cardiac function after AMI.

Bone Marrow Stem Cells Infusion in Treatment of Patients with Acute Myocardial Infarction.

Experimental and clinical data show that bone marrow-derived stem cells (BMSC) can contribute to myocardial regeneration after ischemic injury. We present results of intracoronary infusion of autologous BMSCs in treatment of patients (pts) with acute myocardial infarction (MI). 36 pts with first, anterior wall MI, successfully treated with percutaneous coronary angioplasty were enrolled into the study. 24 pts, aged 50.1±9.05 yrs received intracoronary BMSC infusion 4 to 7 days after MI. Control group consisted of 12 pts, aged 51.6±8.7 yrs. In BMSC group BM in total volume 80 (50–150) ml was collected from iliac crest to buffered saline with heparine. After isolation and 18–24 hrs cultivation BMSCs were resuspended in autologous plasma in final volume 12.25±2.05 ml. The mean number of MNC, CD34+, CD133+/CD45+ and CD133+/CD45− cells were respectively: 0.41±0.18x10e9, 3.89±1.45x10e6, 0.96±0.6x10e6, 0.15±0.1x10e6. Transplanted material was divided into 3–5 portion and injected directly to infarcted area (Strauer method). Left ventricular function was evaluated by echocardiography (contactility index, CI), Tc-99 MIBI SPECT (perfusion index, PI) at rest (R) and with dipiridamol (D) and radionuclide ventriculography (ejection fraction, EF) at baseline and after 3, 6, 12 months (mo). CI and PI were assessed in left ventricle and infarct related artery (IRA) area. Control coronary angiography was performed after 6 mo. No adverse effects of BM aspiration in early MI were observed. One pts revealed chills and fever and 1 acute pulmonary oedema after cell infusion. Control angiography revealed restenosis in 3 pts from BMSC and 2 from control group. Results of cardiac test are presented in table.Conclusions: Intracoronary autologous BMNCs transplantation is safe and feasible. Improvement of left ventricular function was observed in BMSC group, mainly concerning perfusion. No accelerated atherosclerosis was seen after intracoronary BMSC administration.Results of cardiac testsBMSC groupControl grouppCI/CI-IRA 7 day1.62±0.19/2.3±0.361.6±0.24/2.21±0.41nsCI/CI-IRA 3 mo1.55±0.2/2.12±0.41.65±0.3/2.34±0.64nsCI/CI-IRA 6 mo1.5±0.2/2.16±0.371.7±0.29/2.46±0.510.02CI/CI-IRA 12 mo1.55±0.2/2.24±0.441.72±0.33/2.48±0.51nsPi/PI-IRA-R 10 day2.45±0.63/2.96±0.882.45±0.53/3.04±0.74nsPI/PI-IRA-R 3 mo2.25±0.37/2.79±0.612.36±0.44/2.88±0.61nsPI/PI-IRA-R 6 mo2.19±0.43/2.68±0.672.43±0.32/3.02±0.450.07PI/PI-IRA-R 12 mo2.11±0.33/2.63±0.462.36±0.31/2.98±0.46nsPI/PI-IRA-D 10 day2.45±0.63/2.96±0.882.45±0.53/3.04±0.74nsPI/PI-IRA-D 3 mo2.3±0.42/2.87±0.672.43±0.4/2.93±0.44nsPI/PI-IRA-D 6 mo2.2±0.44/2.58±0.832.48±0.43/3.12±0.480.06PI/PI-IRA-D 12 mo2.16±0.43/2.59±0.62.57±0.44/3.35±0.420.009EF 4 day45.0±7.941.6±6.6nsEF 6 mo48.2±9.242.1±11.40.07EF 12 mo48.5±4.938.9±7.70.002

Transcoronary Transplantation of Progenitor Cells after Myocardial Infarction

Pilot studies suggest that intracoronary transplantation of progenitor cells derived from bone marrow (BMC) or circulating blood (CPC) may improve left ventricular function after acute myocardial infarction. The effects of cell transplantation in patients with healed myocardial infarction are unknown. After an initial pilot trial involving 17 patients, we randomly assigned, in a controlled crossover study, 75 patients with stable ischemic heart disease who had had a myocardial infarction at least 3 months previously to receive either no cell infusion (23 patients) or infusion of CPC (24 patients) or BMC (28 patients) into the patent coronary artery supplying the most dyskinetic left ventricular area. The patients in the control group were subsequently randomly assigned to receive CPC or BMC, and the patients who initially received BMC or CPC crossed over to receive CPC or BMC, respectively, at 3 months' follow-up. The absolute change in left ventricular ejection fraction was significantly greater among patients receiving BMC (+2.9 percentage points) than among those receiving CPC (-0.4 percentage point, P=0.003) or no infusion (-1.2 percentage points, P<0.001). The increase in global cardiac function was related to significantly enhanced regional contractility in the area targeted by intracoronary infusion of BMC. The crossover phase of the study revealed that intracoronary infusion of BMC was associated with a significant increase in global and regional left ventricular function, regardless of whether patients crossed over from control to BMC or from CPC to BMC. Intracoronary infusion of progenitor cells is safe and feasible in patients with healed myocardial infarction. Transplantation of BMC is associated with moderate but significant improvement in the left ventricular ejection fraction after 3 months.

Cardiac Stem Cell Therapy

Cardiovascular disease remains the number one cause of morbidity and mortality in the United States and Europe. In the United States alone, ≈1 million patients suffer a myocardial infarction every year, with an associated mortality of 25% at 3 years.1 A more sobering statistic is the fact that there are ≈5 million Americans with congestive heart failure, with an associated 20% mortality per year. This remains the case despite advances in pharmacotherapy, cardiac resynchronization therapies, and the use of implantable cardioverter-defibrillators.2 Some patients with end-stage congestive heart failure are considered for cardiac transplantation, but the demand for this therapeutic approach greatly outweighs the availability of donor hearts. Over the past few years, several animal studies and a few clinical trials have supported the use of stem cells as a potential therapeutic modality to address this unmet clinical need. Response by Boyle et al p 358 Several different types of cells have been used in both animal studies and patients to promote the repair of damaged myocardium. The 2 main sources of stem cells are adult stem and embryonic stem (ES) cells. ### ES Cells ES cells are derived from the inner mass of developing embryos during the blastocyst stage. Characteristic features of ES cells include their proliferative and self-renewing properties and their ability to differentiate into a wide variety of cell types, including cardiac myocytes.3 The major concerns with their use in human trials include the formation of teratomas when ES cells are injected into immunocompromised animals. This is particularly important because the ES cells currently available for use in humans would be of allogeneic origin and therefore would require immunosuppression. As nuclear transfer techniques improve, they will provide a way of generating an unlimited supply of histocompatible ES cells using the nuclei of cells obtained directly from the recipient …

The clinical study of autologous peripheral blood stem cell transplantation by intracoronory infusion in patients with acute myocardial infarction (AMI)

Purpose To investigate the effects and safety of autologous peripheral blood stem cell (PBSCs) transplantation by intracoronory infusion in patients with acute myocardial infarction (AMI). Methods 70 patients with AMI were allocated to two groups, one was PBSCs transplantation group ( n = 35) that received optimal post-infarction medical treatment (standard drug and coronary artery intervention therapy) and intracoronary transplantation of PBSCs; the other was control group ( n = 35) that received optimum post-infarction medical treatment (standard drug and coronary artery intervention therapy). The PBSCs transplantation group received granulocyte colony-stimulating factor (G-CSF: Filgrastim, 300 μg) with the dose of 300–600 μg/day to mobilize the stem cell, and the duration of administration G-CSF was 5 days. On the sixth day, PBSCs were separated by Baxter CS 3000 blood cell separator into suspend liquid 57 ml. Then, the suspend liquid was transferred into the infarct-related artery (IRA) by occluding the over-the-wire balloon and infusing artery through balloon center lumen. In the process of the mobilization, separation and intracoronary infusion of PBSCs, the complications have been investigated. Changes in left ventricular function were assessed at 6-month follow-up. Results 35 cases had finished follow-up in the treated group, while 23 cases in control group. After 6 months, within the treated group, there was a significant improvement in global left ventricular function ejection fraction (EF) from a baseline of 50.0 ± 8.2% to 57.1 ± 7.8% ( P < 0.0001), wall motion score index (WMSI) from 1.219 ± 0.190 to 1.101 ± 0.118 ( P < 0.0001), left end-systolic volume (ESV) from 63.8 ± 23.9 ml to 52.6 ± 20.3 ml ( P = 0.01) and left end-diastolic volume (EDV) from 134.2 ± 36.7 ml to 119.2 ± 30.3 ml ( P = 0.07); in the control group, there was no significant improvement in EF, WISM, EDV and ESV ( P = 0.490, 0.259, 0.117, 0.395). After 6-month follow-up, according to treatment group vs. control group, there was a significant improvement in EF from 57.1 ± 7.8 to 52.6 ± 5.7 ( P = 0.041) and WISM from 1.101 ± 0.118 to 1.184 ± 0.138 ( P = 0.034). There were a total of 25 cases with complications during the mobilization, separating and infusion of PBSC. The incidence of complications relating to mobilization was 37.1% (13/35), relating to separating was 14.3% (5/35) and relating to intracoronary infusion was 20.0% (7/35). No death was observed. Conclusion Autologous PBSCs transplantation by intracoronary infusion is feasible and safe, and it can improve left ventricular function in the 6-month follow-up.

Effect of Intracoronary Transplantation of Autologous Bone Marrow-Derived Mononuclear Cells on Outcomes of Patients With Refractory Chronic Heart Failure Secondary to Ischemic Cardiomyopathy

Recent studies have indicated that stem cell implantation increases cardiac function by repairing damaged myocardium. We investigated whether intracoronary transplantation of autologous bone marrow-derived mononuclear cells (BMMCs) confers beneficial effects in patients with refractory chronic heart failure. Twenty-eight patients received standard heart failure medication and BMMC transplantation (BMMC treatment) or standard medication only (controls). BMMCs were harvested from each patient. Clinical manifestations, biochemical assays, rhythm studies, echocardiograms, and positron emission tomograms were recorded. Fourteen patients with cell grafting had symptomatic relief of heart failure within 3 days. Left ventricular ejection fraction increased by 9.2% and 10.5% at 1 week and 3 months after the procedure, respectively, versus baseline (p < 0.01 for the 2 comparisons). Left ventricular end-systolic volume decreased by 30.7% after 3 months (p < 0.01). Brain natriuretic peptide levels at days 3 and 7 after cell infusion significantly decreased by 69.2% and 70.4%, respectively, whereas atrial natriuretic peptide levels increased by 30.1% at day 7. Positron emission tomographic analysis showed a significant increase in cell viability of 10.3% in the infarcted zone. No patient died in the BMMC-treated group at 6-month follow-up. In contrast, heart failure did not improve in any control patient. Left ventricular ejection fraction decreased by 7.2% after 3 months. Two control patients died from heart failure within 6 months. In conclusion, this is the first demonstration in humans that intracoronary BMMC transplantation is a feasible and safe therapeutic strategy to decrease symptoms, increase cardiac function, and possibly prolong life in patients with end-stage heart failure refractory to standard medical therapy.

Stammzellen nach Myokardinfarkt

Loss of contractile myocardial tissue after myocardial infarction is followed by a remodeling of the left ventricle and clinical manifestation of heart failure, associated with a reduced life expectancy. One possibility to counteract the remodeling process would be to regenerate cardiomyocytes and to improve neovascularization in the infarct area. Indeed, experimental studies demonstrate that transplantation of adult stem or progenitor cells such as circulating, endothelial progenitor cells (CPCs) or progenitor cells derived from the bone marrow, is a therapeutic strategy to improve neovascularization and left ventricular (LV) function after myocardial infarction. First clinical trials in patients after an acute myocardial infarction indicate that intracoronary transplantation of adult progenitor cells is feasible and safe. Furthermore, patients treated with progenitor cells experienced an unexpectedly large improvement of LV function and geometry as well as vascularization, indicating a beneficial effect of the progenitor cell treatment on the postinfarction course. Randomized trials have obtained mixed results with respect to improvement of LV function after intracoronary infusion of progenitor cells, which may be due to methodological differences. However, in the largest trial, REPAIR-AMI, LV function significantly improved in progenitor cell-treated patients compared to a double-blind, randomized placebo-control group. Of note, that trial used a previously validated processing of progenitor cells with respect to in vitro and in vivo progenitor capacity of the cells. The data available, therefore, encourage assessing the efficacy of intracoronary infusion of progenitor cells-established to be efficient in previous trials-after acute myocardial infarction in larger, randomized controlled trials in order to assess the effect on mortality and morbidity.

Stem cell therapy in postinfarction chronic coronary heart disease

After acute myocardial infarction, bone-marrow-derived cells (BMDCs) improve cardiac function; it is conceivable, but not yet demonstrated, that BMDC therapy might also be useful in chronic infarction. We treated 18 consecutive patients who had chronic myocardial infarction (between 5 months and 8.5 years postinfarction) using intracoronary transplantation of autologous BMDCs and compared this group with a representative control group who did not receive cell therapy. After 3 months, infarct size in the transplantation group was reduced by 30% and both global left ventricular ejection fraction and infarction wall-movement velocity were increased significantly (15% and 57%, respectively), whereas in the control group no significant changes were observed. After transplantation of BMDCs, there was an 11% improvement in maximum oxygen uptake and a 15% increase in regional (18)F-fluordeoxyglucose uptake into infarcted tissue, as determined by positron emission tomography. These results show that functional and metabolic regeneration of infarcted and chronically avital tissue can be achieved in humans using transplantation of bone-marrow-derived cells.

Long term follow-up on emergent intracoronary autologous bone marrow mononuclear cell transplantation for acute inferior-wall myocardial infarction

To investigate the effects of emergent intracoronary autologous bone marrow mononuclear cell (BM-MNC) transplantation on left ventricular function and myocardium lesion area in patients with first acute inferior-wall myocardial infarction. Forty patients with first onset of acute inferior-wall myocardial infarction, 28 males and 12 females, aged < or = 75, treated with emergent percutaneous coronary intervention (PCI) were randomly divided into 2 equal groups: group undergoing intracoronary transplantation of autologous BM-MNC via a micro-catheter right after PCI (BM-MNC group), and control group receiving normal saline and heparin. Blood routine examination, myocardium zymogram, and serum high sensitive C reactive protein (hsCRP) were detected, and 24-hour dynamic electrocardiography, delayed-enhancement myocardial magnetic resonance imaging (CMR), and angiography of the coronary artery and left ventricle were conducted before the transplantation and immediately, 1 week, and 6 months after transplantation. CMR showed that 6 months later the left ventricular ejection fraction (LVEF) of the control group was 47.9% +/- 6.7%, significantly higher than that 1 week later (43.4% +/- 6.7%, P = 0.001), and the LVEF of the BM-MNC group 6 months later was 51.5% +/- 5.2%, significantly higher than that 1 week later (44.5% +/- 7.1%, P = 0.001; however, the absolute change of LVEF (DeltaLVEF) of the BM-MNC group was 6.95% +/- 3.33%, significantly higher than that of the control group (4.05% +/- 1.68%, P = 0.047). Six months later the myocardial lesion area of the BM-MNC group decreased more significantly in comparison with the control group. Nevertheless, there was no difference in change of left ventricular end diastolic volume (LVEDV) between these two groups. The serum hsCRP 48 h after transplantation of the BM-MNC group was 2.8 g/L +/- 0.8 g/L, significantly lower than that before transplantation (13.4 g/L +/- 3.6 g/L, P < 0.001). No severe clinical events, such death, recurrent cardiac infarction, malignant arrhythmia, occur in these 2 groups. Emergent intracoronary transplantation of autologous BM-MNC in patients with acute inferior-wall myocardial infarction improves the left ventricular function and myocardial infusion, minimizes the myocardial lesion area significantly.

Complications after intracoronary stem cell transplantation in idiopathic dilated cardiomyopathy

Intracoronary stem cells injection was investigated for myocardial regeneration in patients with ischemic heart disease [1–3]. Its use in idiopathic dilated cardiomyopathy has not been described. A pilot trial testing this method in idiopathic dilated cardiomyopathy was recently started in our institution. We report here unexpected complications in the first two patients. Both had heart failure (left ventricular ejection fraction <35%, NYHA III) and signed informed consent. Radiolabeled autologous bone marrow blood (5 5 ml) was injected through the central lumen of an inflated overthe-wire balloon placed in the proximal LAD. Case no. 1: The patient repeatedly did not tolerate even very short (10 s) balloon inflations: fast blood pressure drop and severe malignant ventricular arrhythmias developed immediately. Thus, the bone marrow blood was injected with a deflated balloon and preserved coronary flow. There were no additional complications, and after balloon catheter withdrawal, coronary angiogram showed normal findings. Patient was discharged home next day. Nevertheless, no myocardial radioactivity was observed at nuclear imaging 24 h after transplantation. Case no. 2: After the experience with the first case, we decided for an undersized balloon not to create complete LAD occlusion. Thus, TIMI-2 flow was preserved during balloon inflations. Four inflations were tolerated well. During the fifth inflation, the patient developed severe hypotension. Angiography showed a severe occlusive

1203 Strain and strain rate imaging to monitor the effect of intracoronary transplantation of labelled mesenchymal stem cells post myocardial infarction in a porcine animal model

1203 Strain and strain rate imaging to monitor the effect of intracoronary transplantation of labelled mesenchymal stem cells post myocardial infarction in a porcine animal model

Regeneration of Human Infarcted Heart Muscle by Intracoronary Autologous Bone Marrow Cell Transplantation in Chronic Coronary Artery Disease: The IACT Study

Stem cell therapy may be useful in chronic myocardial infarction (MI); this is conceivable, but not yet demonstrated in humans. After acute MI, bone marrow-derived cells improve cardiac function. We treated 18 consecutive patients with chronic MI (5 months to 8.5 years old) by the intracoronary transplantation of autologous bone marrow mononuclear cells and compared them with a representative control group without cell therapy. After three months, in the transplantation group, infarct size was reduced by 30% and global left ventricular ejection fraction (+15%) and infarction wall movement velocity (+57%) increased significantly, whereas in the control group no significant changes were observed in infarct size, left ventricular ejection fraction, or wall movement velocity of infarcted area. Percutaneous transluminal coronary angioplasty alone had no effect on left ventricular function. After bone marrow cell transplantation, there was an improvement of maximum oxygen uptake (VO2max, +11%) and of regional 18F-fluor-desoxy-glucose uptake into infarct tissue (+15%). These results demonstrate that functional and metabolic regeneration of infarcted and chronically avital tissue can be realized in humans by bone marrow mononuclear cell transplantation.

Transplantation of Blood-Derived Progenitor Cells After Recanalization of Chronic Coronary Artery Occlusion

Transplantation of blood-derived circulating progenitor cells (CPC) has been shown to improve myocardial regeneration after myocardial infarction. It remains unclear whether CPC transplantation exerts beneficial effects also in patients with chronic myocardial ischemia. We initiated a randomized, double-blind, placebo-controlled study evaluating the impact of intracoronary infusion of CPCs on coronary vasomotion and left ventricular (LV) function in patients after recanalization of chronic coronary total occlusion (CTO). After recanalization of CTO, 26 patients (age, 63+/-2 years; LV ejection fraction, 53+/-2%) were randomly assigned to the treatment (intracoronary transplantation of CPCs) or control group. Coronary flow reserve in response to adenosine (2.4 mg/min) was measured in the target vessel at the beginning of the study and after 3 months. LV function and infarct size were assessed by MRI and metabolism by 18F deoxyglucose positron emission tomography. CPC application resulted in an increase in coronary flow reserve by 43% from 2.3+/-0.3 to 3.3+/-0.5 (P<0.05 versus beginning and control). At 3 months, the number of hibernating segments in the target region (from 2.9+/-0.6 to 2.0+/-0.6 segments, P<0.05 versus beginning and control) had declined in the treatment group, whereas no significant changes were observed in the control group. MRI revealed a reduction in infarct size by 16% and an increase in LV ejection fraction by 14% in the treatment group (from 51.7+/-3.7 to 58.9+/-3.2%; P<0.05 versus beginning and control) because of an augmented wall motion in the target region. Hence, intracoronary transplantation of CPCs after recanalization of CTO results in an improvement of macro- and microvascular function and contributes to the recruitment of hibernating myocardium.

Beware of Cells Bearing Gifts

See related article, pages 159–167 Heart failure is a major worldwide health problem that is growing in prevalence despite recent treatment advances. Patients with heart failure ultimately die from either pump failure or cardiac arrhythmia, and there is a link between the degree of contractile dysfunction and arrhythmic risk. Since the 1960s, the definitive therapy for heart failure has been cardiac transplantation, but the limited supply of organs has restricted the impact of this therapy. Starting in the mid-1990s, a series of observations has led to the concept that cells might be used to repair myocardial damage. Subsequently, this therapy has shown promise in ischemic and nonischemic forms of myocardial injury. The increased availability of cells as compared with organs has driven an exuberant search for the right replacement cells. Nevertheless, after intense study, there is no obvious frontrunner.1 The concept driving the cell selection process has been the need for a sufficient number of immune compatible, contractile cells. Proposed cell sources have included skeletal myoblasts,2 bone marrow–derived progenitor cells,3 and embryonic stem cells.4 These 3 cell types have been shown to improve myocardial function in animal models, and the first 2 have shown promise in human clinical trials.5 Generally, the effects of these 2 cell types on myocardial function have been similar.6 If they are to fulfill their promise as replacement myocytes, it is important that the …

261 Percutaneous intracoronary transplantation of autologous stem cells after acute myocardial infarction. Clinical and angiographic follow-up after 6 months

261 Percutaneous intracoronary transplantation of autologous stem cells after acute myocardial infarction. Clinical and angiographic follow-up after 6 months

Evaluation of intracoronary bone marrow transplantation, in patients with heart failure, by Thallium-201 scintigraphy

Evaluation of intracoronary bone marrow transplantation, in patients with heart failure, by Thallium-201 scintigraphy