A Ghodsizad

Intramyocardial implantation of CD133+ stem cells improved cardiac function without bypass surgery.

INTRODUCTION Cell transplantation for myocardial regeneration has been shown to have beneficial effects on cardiac function after myocardial infarction. Most clinical studies of intramyocardial cell transplantation were performed in combination with coronary artery bypass grafting (CABG). The contribution of implanted stem cells could yet not be clearly distinguished from the effect of the CABG surgery. Our current phase 1 clinical study has focused on the safety and feasibility of CD133+-enriched stem cell transplantation without CABG and its potential beneficial effect on cardiac function. METHOD AND RESULTS Ten patients with end-stage chronic ischemic cardiomyopathy (ejection fraction <22%) were enrolled in the study. Bone marrow (up to 380 mL) was harvested from the iliac crest. CD133+ cells were purified from bone marrow cells using the CliniMACS device with purities up to 99%. Autologous bone marrow CD133+ cells (1.5-9.7 X 106 cells) were injected into predefined regions. Cardiac functions prior to and 3, 6, and 9 months after cell transplantation were assessed by cardiac magnetic resonance imaging. Stem cell transplantation typically improved the heart function stage from New York Heart Association/Canadian Cardiovascular Society class III-IV to I-II. The mean preoperative and postoperative ventricular ejection fractions were 15.8 +/- 5% and 24.8 +/- 5%, respectively. CONCLUSION CD133+ injection into ischemic myocardium was feasible and safe. Stem cell transplantation alone improved cardiac function in all patients. This technique might hold promise as an alternative to medical management in patients with severe ischemic heart failure who are ineligible for conventional revascularization.

Transplanted human cord blood-derived unrestricted somatic stem cells improve left-ventricular function and prevent left-ventricular dilation and scar formation after acute myocardial infarction

Objective: Functional improvement after acute myocardial ischaemia (MI) has been achieved by transplantation of different adult stem and progenitor cell types. It is controversial whether these cell types are able to form novel functional myocardium. Alternatively, graft-related or immune-related paracrine mechanisms may preserve existing myocardium, improve neovascularisation, affect tissue remodelling or induce endogenous de novo formation of functional myocardium. We have applied an alternative somatic cell type, human cord-blood-derived unrestricted somatic stem cells (USSCs) in a porcine model of acute MI. Methods: USSCs were transplanted into the acutely ischaemic lateral wall of the left ventricle (LV). LV dimension and function were assessed by transoesophageal echocardiography (TEE) pre-MI, immediately post-MI, 48 hours and 8 weeks after USSC injection. Additionally, apoptosis, mitosis and recruitment of macrophages were examined 48 hours post-engraftment. Results: Gender-specific and species-specific FISH/immunostaining failed to detect engrafted donor cells 8 weeks post-MI. Nevertheless, cell treatment effectively preserved natural myocardial architecture. Global left ventricular ejection fraction (LVEF) before MI was 60% (7%). Post-MI, LVEF decreased to 34% (8%). After 8 weeks, LVEF had further decreased to 27% (6%) in the control group and recovered to 52% (2%) in the USSC group (p<0.01). Left-ventricular end-diastolic volume (LVEDV) before MI was 28 (2) ml. 8 weeks post-MI, LVEDV had increased to 77 (4) ml in the control group. No LV dilation was detected in the USSC group (LVEDV: 26 (2) ml, p<0.01). Neither apoptosis nor recruitment of macrophages and mitosis were different in either groups. Conclusions: Transplantation of USSCs significantly improved LV function and prevented scar formation as well as LV dilation. Since differentiation, apoptosis and macrophage mobilisation at infarct site were excluded as underlying mechanisms, paracrine effects are most likely to account for the observed effects of USSC treatment.

Autologous bone marrow-derived stem cell therapy in combination with TMLR. A novel therapeutic option for endstage coronary heart disease: report on 2 cases.

We report 2 cases in which patients with coronary heart disease not amenable for conventional revascularization underwent transmyocardial laser revascularization (TMLR) and implantation of AC133+ bone-marrow stem cells. The reason for using TMLR in combination with stem cell application is to take advantage of the synergistic angiogenic effect. The local inflammatory reaction induced by TMLR should serve as an informational platform for stem cells and may trigger their angiogenic differentiation. Functional analysis of myocardial performance after treatment in these 2 cases revealed dramatic improvement of the wall motion at the site of the TMLR and stem cell application. Because TMLR does not enhance myocardial contractility and there was no angiographic evidence of major collaterals to the ischemic region in either patient, we assume that the synergistic effect of stem cells and TMLR-induced angiogenesis occurred; however, our assumption is of a speculative nature. We think that TMLR in combination with stem cell transplantation might become a novel revascularization therapy for ischemic myocardium.

Intraoperative isolation and processing of BM-derived stem cells

To improve tissue regeneration of ischemic myocardium, autologous bone marrow-derived stem cells have been injected intramyocardially in five patients undergoing coronary artery bypass grafting and transmyocardial laser revascularization. An innovative method for the intraoperative isolation of CD133(+)-stem cells in less than 3 hours has been established. After induction of general anesthesia, approx. 60-240 ml of bone marrow were harvested from the posterior iliac crest and processed in the operating room under GMP conditions using the automated cell selection device Clini-MACS. Following standard CABG surgery, LASER channels were shot in predefined areas within the hibernating myocardium. Subsequently, autologous CD133(+)-stem cells (1.9-9.7 x 10(6) cells; purity up to 97%) were injected in a predefined pattern around the laser channels. Through the intraoperative isolation of CD133(+)-cells, this effective treatment of ischemic myocardium can be applied to patients scheduled both for elective and for emergency revascularisation procedures.

Ex vivo coronary angiography of a donor heart in the organ care system.

The international demand for donor hearts for transplantation is steadily increasing. Thus, longer transportation distances and explantation from sites with limited abilities for preexplantation diagnostics have to be considered. The development of the Organ Care System® (OCS) (TransMedics, Andover, MA, USA) may extend the extracorporeal period, with the possibility to constantly evaluate and interact during organ transport. One of the potential advantages of the OCS® is the ability to even perform coronary angiography of the donor heart, if a preexplantation angiography evaluation is not possible at the donor hospital and if significant evidence for coronary artery disease in the donor heart becomes known, because of the donors medical history or after palpation of sclerotic coronary ostia. In this report, we present the first ex vivo coronary angiography evaluation of a potential donor heart that was performed in the OCS®. Upon explantation of the donor heart, sclerosis of the left coronary artery was palpated. After reaching the implantation site, a coronary angiography was performed by placing the OCS® on a catheterization table and inserting a 6F sheath into the access site of the OCS®. A 6F guide catheter was used to intubate the left coronary ostium. Injection of contrast agent led to strong contrast for visualization of the left coronary system. This procedure allowed sufficient assessment of the coronary arteries, which showed a slight diffuse sclerosis without any significant stenosis. This report demonstrates the advantage of the OCS® in the complex assessment of donor hearts after explantation. While the donor heart is still in the OCS®, not only is it possible to measure metabolic parameters and pressures, but even coronary angiography is feasible. With the increasing international demand for donor organs, such ex vivo examinations might play a more important role, because longer transportation distances can be accepted and organs from suboptimal donors without preexplantation diagnostics may be considered at donor sites with limited diagnostic options.

Autologous transplantation of CD133+ BM-derived stem cells as a therapeutic option for dilatative cardiomyopathy

We report the case of a 58-year-old man with end-stage non-ischemic cardiomyopathy. Baseline transthoracic echocardiography (TTE) and cardiac magnetic resonance (cMRI) revealed a markedly depressed left ventricle systolic function. He underwent autologous CD133+ BM-derived cell transplantation through a minimally invasive approach. During surgery 19 x 10(6) BM-derived stem cells were injected by the transepimyocardial route. Six months after the operation TTE and cMRI showed a clear improvement in left ventricular contractility.

A Novel Mechanical Circulatory Approach for Patients with Cardiogenic Shock in the Intensive Care Unit

BACKGROUND The capacity of the heart to maintain cardiac output can be acutely impaired as a result of myocardial infarction, graft failure after transplantation, or other cardiac events. Medical therapy or the use of an intra-aortic balloon pump may be insufficient to help the patient overcome acute cardiogenic shock. The set-up of mechanical assist devices such as extracorporeal membrane oxygenation or patient relocation into the operating room requires valuable time that is often not available. The aim of our study was to test whether a novel left ventricular assist device can be percutaneously implanted without fluoroscopy under echocardiographic navigation in a preclinical model. METHODS Pigs were subjected to percutaneous implantation of a novel left ventricular assist device under navigation of transesophageal echocardiography (TEE) without fluoroscopic support. Percutaneous puncture of the interatrial septum using a Brockenbrough needle and insertion of the afferent cannula into the femoral vein and its advance to the right atrium and through the interatrial septum into the left atrium was performed under echocardiographic control. The efferent cannula was inserted into the contralateral femoral artery using the Seldinger technique. RESULTS In all animals, the percutaneous implantation of a left ventricular assist device was successful under only TEE navigation. CONCLUSIONS The ability to abstain from fluoroscopy and the feasibility of inserting the afferent cannula across the interatrial septum guided by TEE allows for application of this system in intensive care units, saving precious time as well as financial and human resources.

Transfemoral biopsy--a routine procedure after orthotopic heart transplantation for dilated cardiomyopathy in a patient with persistent left superior vena cava and hypoplastic right superior vena cava.

INTRODUCTION The increasing number of end stage heart failure patients has caused a high number of transplant candidates, including patients with concomitant other cardiac abnormalities. Congenital heart failure can exhibit changes in a variety of anatomic landmarks, and performing heart transplantation in this setting can be challenging. Monitoring for possible rejection is done via intramyocardial biopsies. Here the difficulties arise from variations in anatomic structures. BACKGROUND We present a case of a persistent left superior vena cava discovered intraoperatively during heart transplantation. The patient was a 45-year-old man who underwent transplantation for a severely reduced left ventricular function, along with a high left ventricular end-diastolic pressure and and end stage heart failure. DISCUSSION In previous cases, the biopsy was performed by means of left-sided transjugular venous access. Bearing the well-known complications in mind, we chose the transfemoral access so we could take biopsies postoperatively. Biopsies in patients with persistent left vena cava should routinely be performed using the transfemoral access.