Magnetically guided recellularization of decellularized stented porcine pericardium-derived aortic valve for TAVI.

Application of somatic stem cells for growth, proliferation, and differentiation in a three-dimensional pattern is an important aspect in tissue engineering. Here, we report on our bioreactor, which we applied for magnetically guided recellularization of nitinol-stented valve. Human-derived unrestricted somatic stem cells were cultured in medium in our pulsatile dynamic bioreactor for 4-6 days. Stented valves were prepared by decellularization of porcine pericardium and construction of stented tissue-engineered valves (n = 8). A magnetic field was created around the bioreactor to prevent the loss of cells. In the control group, no magnetic device was used (n = 4). Morphological characterization was assessed by immunohistochemical staining of paraffin sections and electron microscopy. The bioreactor enabled the preservation of physiologic culture conditions with aerobic cell metabolism and physiological pH values. Histological analysis showed homogeneous seeding of the pericardium with progenitor cells in the recellularized samples, whereas no cell seeding could be observed in the nonmagnetic group. Our magnetically guided multifunctional bioreactor allows for an efficient three-dimensional culturing of somatic stem cells on decellularized organ-specific matrix.

Clinical application of adult stem cells for therapy for cardiac disease.

INTRODUCTION: Cardiovascular disease is a major cause of death worldwide. Different medical and surgical therapeutic options are well established, but a significant number of patients are not amenable to standard therapeutic options. Cell-based therapies after clinical application have shown different results in recent years. Here, we are giving a comprehensive overview on major available clinical data regarding cell therapy. BACKGROUND: Cell-based therapies and tissue engineering provide new promising platforms to develop upcoming therapeutic options. Initial clinical trials were able to generate promising results. A variety of different stem cell types have been used for the clinical application. Different adult cardiac stem cells and progenitor cells, including mesenchymal, CD34(+) and CD133(+) autologous human bone marrow-derived stem cells (BMCs), human myoblasts, and peripheral blood-derived stem and progenitor cells (PBSCs) have been used for the therapy for end-stage heart failure. Future experiments will show the importance of novel cell populations and clarify the mechanism causing cell therapy-mediated observed effects. CONCLUSION: Several clinical trials have reported on sole therapy, as well as combined application of autologous adult stem cells with conventional revascularization. The reported promising findings encourage further research in the field of the translational research.

Immunosuppression with tacrolimus early after orthotopic heart transplantation: a comparison of prograf and advagraf.

BACKGROUND: We compared trough levels and clinical outcomes in patients who received Prograf or Advagraf (tacrolimus) de novo following heart transplantation surgery. METHODS: Eighty-two patients were included in this follow-up study. Biopsy results were controlled for the first 3 months after orthotopic heart transplantation. Trough levels were monitored for 4 weeks: daily during the first 7 days and once every week thereafter. The lengths of stay in the hospital and in intensive care were compared. The end point of the study was the 1-year mortality rate. RESULTS: We found significant differences between the groups for both biopsy results and trough levels. Trough levels differed for the first 5 days and then converged on the sixth day. The levels remained comparable throughout the monitoring period. The 1-year mortality rates for Prograf and Advagraf were 20% and 15%, respectively. CONCLUSIONS: Trough levels were comparable after an adjustment period. There were no differences between the 2 groups in their 1-year mortality rates. These results suggest that Advagraf is a safe alternative to Prograf for patients who have undergone heart transplantation.

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.

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 donor's 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.

Clinical labeling and imaging of transplanted CD133+/CD34+ stem cells in patients with ischemic heart disease.

The application of somatic stem cells has been shown to support the recovery of the myocardium in end-stage heart failure. A novel method for the intraoperative isolation and labeling of bone marrow-derived stem cells was established. After induction of general anesthesia, up to 400 mL of bone marrow were harvested from the posterior iliac crest and processed in the operating room under good manufacturing practice conditions by means of the automated cell-selection device Clini-MACS (Miltenyi Biotec). We subsequently injected autologous CD133+ and CD34+ stem cells in a predefined pattern around the laser channels in patients undergoing coronary artery bypass surgery and transmyocardial laser procedures. Intraoperative isolation and labeling is an effective cell-separation tool for the future, considering that novel cell markers can be promising new candidates for cell therapy.

Surgical therapy of end-stage heart failure: understanding cell-mediated mechanisms interacting with myocardial damage.

Worldwide, cardiovascular disease results in an estimated 14.3 million deaths per year, giving rise to an increased demand for alternative and advanced treatment. Current approaches include medical management, cardiac transplantation, device therapy, and, most recently, stem cell therapy. Research into cell-based therapies has shown this option to be a promising alternative to the conventional methods. In contrast to early trials, modern approaches now attempt to isolate specific stem cells, as well as increase their numbers by means of amplifying in a culture environment. The method of delivery has also been improved to minimize the risk of micro-infarcts and embolization, which were often observed after the use of coronary catheterization. The latest approach entails direct, surgical, trans-epicardial injection of the stem cell mixture, as well as the use of tissue-engineered meshes consisting of embedded progenitor cells.

Transplanted human cord blood-derived unrestricted somatic stem cells preserve high-energy reserves at the site of acute myocardial infarction.

BACKGROUND AIMS: It has been demonstrated that transplantation of human cord blood-derived unrestricted somatic stem cells (USSC) in a porcine model of acute myocardial infarction (MI) significantly improved left ventricular (LV) function and prevented scar formation as well as LV dilation. Differentiation, apoptosis and macrophage mobilization at the infarct site could be excluded as the underlying mechanisms. The paracrine effect of the cells is most likely to be observed as the cause for the USSC treatment. The aim of our study was to examine the cardiomyocyte metabolism and the role of high-energy phosphates at the marginal infarct. Methods. USSC were transplanted into the myocardium of the LV, which was supplied by a ligated circumflex artery. Forty-eight hours later, the hearts were harvested and biopsies were performed from the marginal infarct zone surrounding the site of the cell injection. The concentrations of creatinine phosphate (CP), adenosine monophosphate (AMP), adenosine diphosphate (ADP) and adenosine triphosphate (ATP) were determined by chromatography. RESULTS: The concentration of ADP, ATP and CP in the marginal zone of the infarction was significantly higher in the USSC group. The mean global left ventricular ejection fraction (LVEF) (SD) was 64% (8%) before MI; post-MI, LVEF decreased to 35% (9%). CONCLUSIONS: Preservation of high-energy phosphates in the marginal infarct zone suggests that the preservation of energy reserves of surviving cardiomyocytes is a possible mechanism of action of transplanted stem cells in acutely ischemic myocardium.

Management of biventricular assist device implantation in patients with necrotic pancreatitis.

This report describes the management of biventricular assist device (BIVAD) implantation in a patient with necrotic pancreatitis. BIVADs provide mechanical support for ventricular ejection in the failing heart and have become an accepted treatment for end-stage heart failure. They also have proved to be a successful bridge to heart transplantation. As their popularity has grown, the number of patients with BIVADs presenting for noncardiac surgery is increasing. We report the successful management of an implanted extracorporeal BIVAD in a patient with end-stage heart failure and with pancreatic stents in a case of necrotic pancreatitis. Historical, physical, laboratory, and imaging data allowed conservative management leading to a favorable outcome.