Current state of the art in myocardial tissue engineering

Myocardial tissue engineering aims to repair, replace, and regenerate damaged cardiac tissue using tissue constructs created ex vivo. This approach may one day provide a full treatment for several cardiac disorders, including congenital diseases or ventricular dysfunction after myocardial infarction. Although the ex vivo construction of a myocardium-like tissue is faced with many challenges, it is nevertheless a pressing objective for cardiac reparative medicine. Multidisciplinary efforts have already led to the development of promising viable muscle constructs. In this article, we review the various concepts of cardiac tissue engineering and their specific challenges. We also review the different types of existing biografts and their physiological relevance. Although many investigators have favored cardiomyocytes, we discuss the potential of other clinically relevant cells, as well as the various hypotheses proposed to explain the functional benefit of cell transplantation.     

The evolution of vascular tissue engineering and current state of the art

Dacron? (polyethylene terephthalate) and Goretex? (expanded polytetrafluoroethylene) vascular grafts have been very successful in replacing obstructed blood vessels of large and medium diameters. However, as diameters decrease below 6 mm, these grafts are clearly outperformed by transposed autologous veins and, particularly, arteries. With approximately 8 million individuals with peripheral arterial disease, over 500,000 patients diagnosed with end-stage renal disease, and over 250,000 patients per year undergoing coronary bypass in the USA alone, there is a critical clinical need for a functional small-diameter conduit [Lloyd-Jones et al., Circulation 2010;121:e46-e215]. Over the last decade, we have witnessed a dramatic paradigm shift in cardiovascular tissue engineering that has driven the field away from biomaterial-focused approaches and towards more biology-driven strategies. In this article, we review the preclinical and clinical efforts in the quest for a tissue-engineered blood vessel that is free of permanent synthetic scaffolds but has the mechanical strength to become a successful arterial graft. Special emphasis is given to the tissue engineering by self-assembly (TESA) approach, which has been the only one to reach clinical trials for applications under arterial pressure.     

Engineering the heart piece by piece: state of the art in cardiac tissue engineering

According to the National Transplant Society, more than 7000 Americans in need of organs die every year owing to a lack of lifesaving organs. Bioengineering 3D organs in vitro for subsequent implantation may provide a solution to this problem. The field of tissue engineering in its most rudimentary form is focused on the developed of transplantable organ substitutes in the laboratory. The objective of this article is to introduce important technological hurdles in the field of cardiac tissue engineering. This review starts with an overview of tissue engineering, followed by an introduction to the field of cardiovascular tissue engineering and finally summarizes some of the key advances in cardiac tissue engineering; specific topics discussed in this article include cell sourcing and biomaterials, in vitro models of cardiac muscle and bioreactors. The article concludes with thoughts on the utility of tissue-engineering models in basic research as well as critical technological hurdles that need to be addressed in the future.     

Malaria: state of art

Some actual aspects of malaria are here described. After an outline of the actual epidemiological situation of malaria endemic in the world and some historical reports on Italian malaria phenomena before the institution of malaria control measures, chemoprophylaxis and its more problematic aspects, mainly related to multiresistant drug Plasmodium falciparum strains, are discussed in the first part. In the second part the factors potentially implicated in a reintroduction of malaria in free areas are analyzed; with a special reference to climatic changes. Finally the more recent vaccine perspectives are summarized; the authors discuss the principal experiences made using synthetic peptides of different plasmodial origin.     

Myoelectric prostheses: state of the art

The following is a brief introduction to powered prosthetics and myoelectric control. This paper reviews the present availability and clinical impact of myoelectric prostheses. A significant observation is that these systems have reached a sufficient degree of maturity that they are accepted by many health-care funding agencies as reasonable and cost-effective components of the rehabilitation process. The limitations of both the mechanical systems and the myoelectric controls are discussed in some detail, from the viewpoint of the potential user. Finally, an overview is given of current research in this field with comments on probable directions of development.     

Mastocytosis: state of the art.

Mastocytosis is a neoplastic disease involving mast cells (MC) and their CD34+ progenitors. Symptoms in mastocytosis are caused by biological mediators released from MC and/or the infiltration of neoplastic MC in various organs, the skin and the bone marrow being predominantly involved. A WHO consensus classification for mastocytosis exists, which is widely accepted and includes three major categories: (1) Cutaneous mastocytosis (CM), a benign disease in which MC infiltration is confined to the skin, is preferentially seen in young children and exhibits a marked tendency to regress spontaneously. (2) Systemic mastocytosis (SM) which is commonly diagnosed in adults and includes four major subtypes: (i) indolent SM (ISM, the most common form involving mainly skin and bone marrow); (ii) a unique subcategory termed SM with an associated non-mast cell clonal hematological disease (SM-AHNMD); (iii) aggressive SM usually presenting without skin lesions, and (iv) MC leukemia, probably representing the rarest variant of human leukemias. (3) The extremely rare localized extracutaneous MC neoplasms, either presenting as malignancy (MC sarcoma) or as benign tumor termed extracutaneous mastocytoma. Diagnostic criteria for mastocytosis are available and are widely accepted. SM criteria include one major criterion (multifocal compact tissue infiltration by MC) and four minor criteria: (1) prominent spindling of MC; (2) atypical immunophenotype of MC with coexpression of CD2 and/or CD25 (antigens which have not been found to be expressed on normal/reactive MC); (3) activating (somatic) point mutations of the c-kit proto-oncogene usually involving exon 17, with the imatinib-resistant type D816V being most frequent, and (4) persistently elevated serum tryptase level (>20 ng/ml). To establish the diagnosis of SM, at least one major and one minor criterion, or at least three minor criteria, have to be fulfilled. The natural clinical course of mastocytosis is variable. Most patients, in particular those with CM and ISM, remain in an indolent stage over many years or even decades, while others, in particular those with aggressive SM, SM-AHNMD, or mast cell leukemia, show a progressive course, usually with a fatal outcome.     

Autoimmune prostatitis: state of the art

The prostate is one of the main male sex accessory glands and the target of many pathological conditions affecting men of all ages. Pathological conditions of the prostate gland range from infections, chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) of a still unknown aetiology to benign hyperplasia and cancer. CP/CPPS is one of the most prevalent diseases in the urologic clinic and affects men younger than 50 years old. A significant advance in the understanding of CP/CPPS was made when an autoimmune response against prostate antigens was revealed in a considerable number of patients. During the last 30 years, extensive work has been done regarding the development and characterization of different rodent models of experimental autoimmune prostatitis (EAP). It has been demonstrated that tolerance to prostate antigens can be disrupted in some strains of rats and mice and cellular and humoral responses to prostate antigens are elicited. A Th1 pattern has been described and the cellular response seems to be the major pathogenic mechanism involved. Immune cells infiltrate the gland and induce prostate lesions. The genetic background and hormonal imbalance are factors that could contribute to the onset of the disease in susceptible young males. Moreover, spontaneous autoimmune prostatitis could also occur with advanced age in susceptible strains. In this review, we summarize the current knowledge regarding rodent models of EAP and the immunological alterations present in CP/CPPS patients. We also discuss the reliability of these experimental approaches as genuine tools for the study of human disease.     

Cardiovascular tissue engineering: a new laminar flow chamber for in vitro improvement of mechanical tissue properties

A new in vitro flow system was developed to investigate the impact of laminar flow on extracellular matrix formation and tissue development. The dynamic in vitro system was designed to provide a cross flow arrangement of main flow induced by a dialysis roller pump (500 ml/min), and nutrition flow by a perfusion pump (3 ml/hr). Poly-L-lysine precoated polyglycolic acid (PGA) scaffolds (3.14 cm2) were seeded with myofibroblasts of human aortic origin (3.0 x 10(6) cells/ mesh) and incubated for 14 days under static conditions. The tissue was exposed to shear stress over a time period of 14 days (n = 4). The control group was seeded under static conditions (n = 4). To obtain a CO2 independent medium, 25 mM HEPES and 1 mM bicarbonate buffer was supplemented to modified MEM without bicarbonate. Gas samples were collected from the medium, and hydroxyproline assay was performed as a marker of collagen production. The newly developed flow system maintained stable cell culture conditions, with the hydroxyproline concentration significantly higher in group F (p < 0.05). These preliminary experiences with a new in vitro tissue culture system demonstrate the feasibility of using flow induced mechanical stress to enhance extracellular matrix formation.     

Cardiovascular physiology during fetal development and implications for tissue engineering

Shear stress in fluid dynamics has a well-known impact on vascular cell morphology, proliferation, orientation, and the organization and composition of extracellular matrix. There is an increasing interest in the field of tissue engineering to use defined shear stress in bioreactors for tissue conditioning and guided tissue formation. Especially for cardiovascular structures like heart valves or blood vessels, the type and appropriate amount of shear stress needed to improve tissue formation remains speculative. The authors believe that fetal-like conditions may be more optimal for new tissue formation in a bioreactor. The purpose of this review is to delineate parameters of cardiovascular physiology during embryonic and fetal development that may have a potential impact on the design and setting of bioreactors for cardiovascular tissue engineering.     

Emergence of cooperation: state of the art

This review presents a review of prevalent results within research pertaining to emergent cooperation in biologically inspired artificial social systems. Results reviewed maintain particular reference to biologically inspired design principles, given that current mathematical and empirical tools have provided only a partial insight into elucidating mechanisms responsible for emergent cooperation, and then only in systems of an abstract nature. This review aims to provide an overview of important and disparate research contributions that investigate utilization of biologically inspired concepts such as emergence, evolution, and self-organization as a means of attaining cooperation in artificial social systems. An introduction and overview of emergent cooperation in artificial life is presented, followed by a survey of emergent cooperation in swarm-based systems, the pursuit-evasion domain, and RoboCup soccer. The final section draws conclusions regarding future directions of emergent cooperation as a problem-solving methodology that is potentially applicable in a wide range of problem domains. Within each of these sections and their respective themes of research, the mechanisms deemed to be responsible for emergent cooperation are elucidated and their key limitations highlighted. The review concludes that current studies in emergent cooperative behavior are limited by a lack of situated and embodied approaches, and by the research infancy of current biologically inspired design approaches. Despite these limiting factors, emergent cooperation maintains considerable future potential in a wide variety of application domains where systems composed of many interacting components must cooperatively perform unanticipated global tasks.     

Uremic toxicity: present state of the art

The uremic syndrome is a complex mixture of organ dysfunctions, which is attributed to the retention of a myriad of compounds that under normal condition are excreted by the healthy kidneys (uremic toxins). In the area of identification and characterization of uremic toxins and in the knowledge of their pathophysiologic importance, major steps forward have been made during recent years. The present article is a review of several of these steps, especially in the area of information about the compounds that could play a role in the development of cardiovascular complications. It is written by those members of the Uremic Toxins Group, which has been created by the European Society for Artificial Organs (ESAO). Each of the 16 authors has written a state of the art in his/her major area of interest.     

Sudden cardiac death: state of the art

Sudden cardiac death (SCD) is an integral term for several heart diseases among which SCD caused by ischemic heart disease (IHD) designated as sudden coronary death (SCD) ranks first. SCD associated with alcoholic cardiomyopathy ranks second. Risk factors and pathologic manifestations of SCD correspond to those of IHD, atherosclerosis, myocardial infarction. Cardiac arrest takes place because of fibrillation of ventricular myocardium. Factor inducing fibrillation is an advanced irreversable myocardial ischemia complicated with reperfusion. The latter promotes elimination of arrythmogenic substances from the ishemic zone leading to electric unstability of the myocardium and fatal arrythmia. Possibility of idiopathic ventricular fibrillation and its mechanisms is discussed.