Stem cell sources for regenerative medicine: the immunological point of view

Stem cell transplantation consists in the introduction of stem cells or derived products in a diseased organism. Because of the differentiation properties of stem cells, the goal is to replace damaged cells or tissues. Numbers of stem cell were identified and isolated from embryos, fetuses, or adult organs, harboring different properties, and thus providing multiple strategies of regenerative medicine for different diseases. More recently, the artificial induction of stemness properties in adult somatic cells has proposed a new way to generate stem cells. One important concern of stem cell therapy is the possible risk that transplanted stem cells could be rejected by the recipient's immune system. Depending on their source, stem cell transplantation is associated with diverse immunological situations. If some sources allow autologous transplantation, others cannot bypass an allogeneic context between the donor and the recipient. This review summarizes all of the stem cell sources for regenerative medicine and the immunological questions associated to their use. Regarding the emerging strategies compatible with autologous transplantation, this article points notably the complexity of the choice between the immunological safety and the specific advantages of allogeneic stem cell

Aging and Infectious Diseases in the Developing World

Although demographic aging does not remain restricted to industrialized countries, the medical challenge arising from the aging population will be distinct in the developing world. This is particularly true with respect to infectious diseases, which have a distinct spectrum in the elderly population, as well as a greater overall relevance in the developing world. Tropical diseases have a specific presentation and epidemiology in elderly patients. Infectious diseases with a worldwide distribution impact elderly patients in the developing world in a specific manner, which is most obvious with respect to human immunodeficiency virus and tuberculosis but is also true with respect to "trivial” manifestations of infection, such as diarrhea and pneumonia. Malnutrition contributes in a major way to the immunodeficiency of elderly patients in the developing world. Poorly controlled use of antimicrobial drugs leads to multidrug-resistant microorganisms, which, together with the limited resources available for drug treatment, makes appropriate treatment of infections in elderly patients in developing countries very difficult. Infections in elderly patients will have an increasing impact on the public health and economy of developing countrie

Targeting NOX enzymes in the central nervous system: therapeutic opportunities

Among the pathogenic mechanisms underlying central nervous system (CNS) diseases, oxidative stress is almost invariably described. For this reason, numerous attempts have been made to decrease reactive oxygen species (ROS) with the administration of antioxidants as potential therapies for CNS disorders. However, such treatments have always failed in clinical trials. Targeting specific sources of reactive oxygen species in the CNS (e.g. NOX enzymes) represents an alternative promising option. Indeed, NOX enzymes are major generators of ROS, which regulate progression of CNS disorders as diverse as amyotrophic lateral sclerosis, schizophrenia, Alzheimer disease, Parkinson disease, and stroke. On the other hand, in autoimmune demyelinating diseases, ROS generated by NOX enzymes are protective, presumably by dampening the specific immune response. In this review, we discuss the possibility of developing therapeutics targeting NADPH oxidase (NOX) enzymes for the treatment of different CNS pathologies. Specific compounds able to modulate the activation of NOX enzymes, and the consequent production of ROS, could fill the need for disease-modifying drugs for many incurable CNS pathologie

The NADPH oxidase NOX2 plays a role in periodontal pathologies

Oxidative stress plays an important role in periodontal health and disease. The phagocyte nicotinamide adenine dinucleotide phosphate oxidase NOX2 is most likely one of the key sources of reactive oxygen species (ROS) in periodontal tissues. This review will discuss three clinical aspects of NOX2 function. We will first focus on oral pathology in NOX2 deficiency such as chronic granulomatous disease (CGD). CGD patients are thought to suffer from infections and sterile hyperinflammation in the oral cavity. Indeed, the periodontium appears to be the most common site of infection in CGD patients; however, as periodontitis is also common in the general population, it is not clear to which extent these infections can be attributed to the disease. Secondly, the role of oxidative stress in periodontal disease of diabetic patients will be reviewed. Diabetes is indeed a major risk factor to develop periodontal disease, and increased activity of leukocytes is commonly observed. Enhanced NOX2 activity is likely to be involved in the pathomechanism, but data remains somewhat preliminary. The strongest case for involvement of NOX2 in periodontal diseases is aggressive periodontitis. Increased ROS generation by leukocytes from patients with aggressive periodontitis has clearly been documented. This increased ROS generation is to be caused by two factors: (1) genetically enhanced ROS generation and (2) oral pathogens that enhance NOX function. NOX enzymes in the oral cavity have so far received little attention but are likely to be important players in this setting. New therapies could be derived from these new concept

Hyperinflammation in chronic granulomatous disease and anti-inflammatory role of the phagocyte NADPH oxidase

Chronic granulomatous disease (CGD) is an immunodeficiency caused by the lack of the superoxide-producing phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. However, CGD patients not only suffer from recurrent infections, but also present with inflammatory, non-infectious conditions. Among the latter, granulomas figure prominently, which gave the name to the disease, and colitis, which is frequent and leads to a substantial morbidity. In this paper, we systematically review the inflammatory lesions in different organs of CGD patients and compare them to observations in CGD mouse models. In addition to the more classical inflammatory lesions, CGD patients and their relatives have increased frequency of autoimmune diseases, and CGD mice are arthritis-prone. Possible mechanisms involved in CGD hyperinflammation include decreased degradation of phagocytosed material, redox-dependent termination of proinflammatory mediators and/or signaling, as well as redox-dependent cross-talk between phagocytes and lymphocytes (e.g. defective tryptophan catabolism). As a conclusion from this review, we propose the existence of ROShigh and ROSlow inflammatory responses, which are triggered as a function of the level of reactive oxygen species and have specific characteristics in terms of physiology and pathophysiolog