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Biomedical subjects

Harald C Ott

Publications and source records attributed to Harald C Ott.

7 recordsLinked to original sources
PubMed2007

The adult human heart as a source for stem cells: repair strategies with embryonic-like progenitor cells.

Adequate cell-based repair of adult myocardium remains an elusive goal because most cells that are used cannot generate mature myocardium sufficient to promote large functional improvements. Embryonic stem cells can generate both mature cardiocytes and vasculature, but their use is hampered by associated teratoma formation and the need for an allogeneic source. The detection of sca-1(+), c-kit(+), or isl-1(+) cardiac precursors and the creation of cardiospheres from adult heart tissues suggest that a persistent population of immature progenitor cells is present in the mature myocardium. These cell populations probably represent stages along a continuum of cardiac stem cell development and differentiation. We report isolation from ventricle of uncommitted cardiac progenitor cells, which appear to resemble the more immature, common pool of embryonic lateral plate mesoderm progenitors that yield both myocardial and endocardial cells during normal cardiac development. Under controlled in vitro conditions and in vivo, these cells can differentiate into endothelial, smooth muscle, and cardiomyocyte lineages and can be isolated and expanded to clinically relevant numbers from adult rat myocardial tissue. In this article, we discuss the potential for autologous repair or even cardiac regeneration with cells that follow a developmental pathway similar to embryonic cardiac precursors but without the inherent limitations associated with undifferentiated embryonic stem cells.

Adult↗
PubMed2006

From cardiac repair to cardiac regeneration--ready to translate?

Cardiovascular disease is a major public health challenge in the western world. Mortality of acute events has improved, but more patients develop HF--a condition affecting up to 22 million people worldwide. Cell transplantation is the first therapy to attempt replacement of lost cardiomyocytes and vasculature to restore lost contractile function. Since the first reported functional repair after injection of autologous skeletal myoblasts into the injured heart in 1998, a variety of cell types have been proposed for transplantation in different stages of cardiovascular disease. Fifteen years of preclinical research and the rapid move into clinical studies have left us with promising results and a better understanding of cells as a potential clinical tool. Cell-based cardiac repair has been the first step, but cardiac regeneration remains the more ambitious goal. Promising new cell types and the rapidly evolving concept of adult stem and progenitor cell fate may enable us to move towards regenerating viable and functional myocardium. Meeting a multidisciplinary consensus will be required to translate these findings into safe and applicable clinical tools.

Animals↗
PubMed2005

Intramyocardial microdepot injection increases the efficacy of skeletal myoblast transplantation.

OBJECTIVE: Recent progress in the field of cellular cardiomyoplasty has opened new prospects for the treatment of ischemic heart disease and currently moves from bench to bedside. The aim of the present study was to develop a novel cell delivery technique, reducing target tissue damage and improving cell dispersion and engraftment. METHODS: In 30 male Fischer F344 rats an infarction of the left ventricle was generated by ligation of the left anterior descendent artery. Seven days after infarction, either 15 microdepots of 10 microl myoblast cell suspension (microdepot group) or culture medium (control group) were injected into the infarcted region using an automatic pressure injection device, or three depots of 50 microl myoblast cell suspension (macrodepot group) were injected using the standard surgical technique. Echocardiography was performed in all rats before and 6 weeks after cell injection. In all groups the perioperative mortality was below 20%. Six weeks after cell transplantation, a significant improvement of ejection fraction was seen in both myoblast treated groups compared to controls (macrodepot, microdepot, control; 53.7+/-11.9, 70.7+/-2.0, 39.1+/-6.4; P=0.026, P<0.001). The microdepot group showed a more decent improvement than the macrodepot group (70.7+/-2.0 vs. 53.7+/-11.9, P=0.013). In both treated groups, grafted myoblasts differentiated into multinucleated myotubes within host myocardium, however, the engraftment pattern was different and angiogenesis was enhanced in the microdepot group. CONCLUSIONS: Intramyocardial multisite pressure injection allows the safe and reliable transplantation of several myoblast microdepots into an infarcted myocardium and improves the efficacy of myoblast transplantation compared to the standard technique.

Animals↗
PubMed2005

Cell therapy for heart failure--muscle, bone marrow, blood, and cardiac-derived stem cells.

Heart failure (HF) affects a rapidly growing population of patients. Despite improvements in the understanding and therapy of many stages of cardiovascular disease, there has been little progress in treating HF. In the late-stage disease, current options are cardiac transplantation and mechanical support--options that are limited to a small patient collective. The ischemically injured failing heart lacks contractile myocardium, functional vasculature, and electrical integrity, which has made treatment of the underlying injury untenable in the past. Restoring all of these components seems an overwhelming challenge. Yet, the concept of cell therapy--tissue repair by transplantation of stem and progenitor cells--has opened new potential options for patients with heart failure. Skeletal myoblasts, bone marrow, and blood-derived stem cells have all shown considerable myogenic and angiogenic potential in vitro and have rapidly moved from bench to bedside. A number of nonrandomized, non-placebo-controlled safety and feasibility studies have been reported and now double-blinded randomized controlled trials are underway. Despite this rapid clinical pace, the exact mechanisms underlying the functional benefits of different cell types are not well understood. Instead, multiple similar mechanism have been ascribed to virtually every cell type. Thus, while the field is exciting and offers unheralded promise to treat patients with CVD, we must proceed with due diligence and caution. Only a deep understanding of the benefits versus the risks, and the mechanisms involved in cell-mediated cardiac repair, will allow us to design clinically valuable tools and fulfill the potential of this exciting 21st century approach to treating cardiovascular disease.

Animals↗
PubMed2004

Respiratory symptoms and bronchoalveolar lavage abnormalities in molybdenum exposed workers.

STUDY OBJECTIVES: To detect an adverse effect of chronic inhalative molybdenum trioxide (MoO3) exposure in a group of symptomatic MoO3 exposed workers. PARTICIPANTS: 43 inhalatively MoO3 exposed workers of a metal plant and 23 non-exposed controls were included in this study. Among the workers, 33 suffered from respiratory symptoms while 10 individuals were asymptomatic. INTERVENTIONS: Chest x-ray, spirometry and bronchoalveolar lavage (BAL) were performed using standard equipment. MEASUREMENTS AND RESULTS: Neither symptomatic nor asymptomatic MoO3 exposed workers showed firm radiological signs of interstitial lung disease. In lung function testing, symptomatic MoO3 exposed workers did not differ from their asymptomatic colleagues. Employees of the metal plant had a higher percentage of predicted forced expiratory volume in 1 second (FEV1 %) and a higher percentage of predicted forced vital capacity (FVC %) than controls (p<0.05). In BAL cytology, symptomatic MoO3 exposed workers showed higher percentage counts of lymphocytes (p < 0.001) and neutrophils (p < 0.01), and higher T4/T8 ratios (p < 0.01) than asymptomatic MoO3 exposed workers. Furthermore symptomatic workers showed higher percentage counts of lymphocytes (p < 0.05) and neutrophils (p < 0.05) than individuals of the control group. CONCLUSION: The results of BAL cytology in symptomatic workers may be interpreted as a MoO3 induced subclinical alveolitis. This may indicate an adverse effect of chronic inhalative MoO3 exposure. It remains unclear whether symptomatic MoO3 exposed workers are at risk for the development of an interstitial lung disease in the future.

Adolescent↗