Chronic granulomatous disease is a genetic disorder responsible for a defect in the NADPH oxidase of phagocytic cells. It impairs the oxidative burst necessary to the intracellular inactivation of microorganisms and predisposes to an increased risk of infections by various microorganisms, including fungi like Aspergillus spp. and other less frequently encountered or emerging fungal species. Here we review the genetic basis, pathogenesis and clinical presentation associated with fungal infections in chronic granulomatous disease as well as the current prophylaxis and newly available therapies.

The bioethics law of 2004 prohibited any research on the human embryo but authorized by way of derogation this one. The French biomedicine agency was charged to take care of the scientific, legal respect and ethics of this research, via its council of orientation. In 5 years it took more than 100 decisions on this subject. Although the discussions for the revision were important these last years, the new law of bioethics of July 7th, 2011 does not change anything with regard to research on the embryo and the stem cells.

Normal spermatogenesis results from a balance between process of cell proliferation, cell differentiation and apoptosis that concern somatic cells and germ cells. Dysfunction of spermatogenesis may be the result of constitutional or acquired abnormalities of spermatogonia stem cells or somatic cells. To overcome these problems, it seems necessary to implement preventive measures for germ stem cell preservation or substitute measures to replace them, the objective being to replicate in vivo or in vitro the process of spermatozoa production. This article will discuss the different experimental strategies for considering the in vivo or in vitro production of spermatozoa, outside the physiological process.

Preimplantation genetic diagnosis (PGD) has been practiced for over 20 years. It prevents the birth of children with serious genetic diseases by selecting healthy embryos before pregnancy. In France, the initial indications of PGD have been extended in two directions: on the one hand, to allow identification of a mutation combined with embryo's HLA typing, to obtain, at birth, stem cells for therapeutic purposes, and on the other hand, to avoid transmission of late onset diseases without having to test the at-risk parent. Other applications are practiced worldwide but are not allowed in our country, such as social sexing. Technological developments can enable more complex diagnosis, research of several diseases or other genetic traits. It may be useful, for example, to use this possibility to add screening for Down's syndrome at any PDG in older women, when the risk is high. Other objectives were considered but presenting difficulties in their application, not only for regulatory and technical reasons, but also from an ethical point of view.

Acute megakaryoblastic leukemia accounts for approximately 3-10% of acute myeloid leukemia in children. Its diagnosis may be difficult because of associated myelofibrosis. We report the case of a 7-month-old child who presented hepatomegaly with bicytopenia. She also developed bone and joint pain with recurrent aseptic arthritis. We suggested the diagnosis of megakaryoblastic leukemia early but multiple bone marrow investigations had been processed without positive results because of sampling problems and lack of abnormal cells in the morphological, phenotypic, and cytogenetic examinations. We had a variety of indirect evidence for our assumption: the x-ray showing periosteal new bone, lytic lesions and metaphyseal bands, bone marrow aspirate smears with micromegakaryocytes, and bone marrow biopsy suggesting myelofibrosis. This was very suggestive of leukemia but we could not prove it and we finally found megakaryoblasts on bone marrow aspirate smears after more than 2 months of investigation and initiated a course of corticosteroids.

Diffuse Large B Cells Lymphoma (DLBCL) is the most common non-Hodgkin lymphoma and comprises a large number of different entities with different clinico-pathological characteristics. The role of positron emission tomography is essential during the initial staging and post treatment assessment, and potentially at early- or mid-treatment evaluation of response. First line therapy comprises immuno-chemotherapy with rituximab and different cytotoxic agents that differ for components, dosages and frequency of administration taking worldwide-recognized pre-treatment prognostic variables into account. After relapse, peripheral blood stem cells transplantation remains the only chance of cure. This review attempts to summarize the current state of our knowledge by highlighting the leads pursued to further improve current therapeutic results.

Stem cells discovery and their potential have led to the emergence of new forms of therapy with the development of bio-engineering cell and tissue methods underlying future medicine. The availability of stem cells and their preservation thus become an issue for everyone's health. Among the different sources of stem cells, those in the dental pulp have the advantage of being pluripotent, they can be cryopreserved and stored for long periods without losing their multiplication and differentiation capacities and finally they are easily accessible. The wisdom or natal teeth extracted for medical reasons are an opportunity for everyone to preserve stem cells for an autologous use. Biobanks authorized and specialized in the preparation and storage of pulp stem cells provide access to autologous regenerative medicine of tomorrow.

Recent societal evolutions have enabled more and more men to talk about erectile dysfunction (ED). There is a strong association between ED and cardiovascular disease and ED should now be considered as an early clinical evidence of vascular disorder. Inhibitors of the PDE-5 have revolutionized the treatment of ED. The three currently drugs (sildenafil, vardenafil and tadalafil) available as first-line therapeutic option, are well tolerated and highly effective in improving erectile function. All the potential cardiac and vascular effects of PDE-5 inhibitors have recently been reviewed. Despite the fact that million patients with ED worldwide have been successfully treated with one of these PDE5 inhibitors, some men are always difficult to treat. Several new PDE-5 inhibitors have recently been developed and are now being investigated in trials. However 30% of patients need alternative therapies and intracavernous injections are the most successful second-line treatment. Some of new therapeutic approaches are currently under investigation such as gene transfer therapy and stem cells therapy, melanocortin activators or extracorporeal shockwave therapy. Such approaches are still at an early stage but remain exciting new targets in difficult to treat patients.

Lung transplantation is still the only curative treatment for end-stage pulmonary diseases. The results remain poor, however, because of the limited availability of lung donors, chronic rejection, and complications related to immunosuppressive therapy. The use of a bioartificial lung generated from autologous cells could offer a solution. We have demonstrated that in vivo epithelial and cartilage regeneration of the airways is feasible with the use of an aortic tissue matrix. Other studies show that in vitro and in vivo airway regeneration, respectively, can be obtained by using bio-engineering and heterotopic allograft implantation. A more complex challenge is the creation of an artificial lung Indeed, this would require the use of an elastic matrix that can promote regeneration of the different lung components (airways, alveoli, vessels) over a large surface area, thus allowing ventilation, blood perfusion and gas exchanges. Recent studies have demonstrated the possibility of in vitro and in vivo regeneration of lung tissue from autologous cells, and especially stem cells. This emerging research field is currently dominated by the use of decellularized lung matrices and autologous epithelial and endothelial cells. Implantation of such a recellularized matrix in animals has proved the feasibility of a functional bio-artificial lung. The first human transplantation of a bio-artificial lung should be possible within 10-20 years.

The growing incidence of heart failure and the limitations of cardiac transplantation and totally implantable artificial hearts justify the search for alternative therapies. Self-reconstruction of the heart might be one of them. It is based on the use of an animal-derived decellularized scaffold reseeded with cells able to reconstitute a contractile, vascular and valvular pattern affording normal cardiac function. Whereas decellularization techniques are currently well controlled, the choice of cell type to generate the different constituents of cardiac tissue (cardiomyocytes, endothelial cells, smooth vascular cells, myofibroblasts), and the optimal mode of cell transfer, are still far from clear. Furthermore, scaffold recolonization is not only dependent on the phenotype of the grafted cells: it is also influenced by the nature of the biochemical signals emitted by the scaffold and by the physical state of the substrate. Modulation of these two factors can influence the contractile performance of the self-rebuilt organ. The complexity of these challenges is such that total replacement of the heart by a self-built organ is at best a far-off perspective. However, continued pursuit of this objective stimulates the development of bioengineering techniques, and partial replacement of heart tissue by cell-seeded scaffolds appears more feasible. Applications could include the strengthening of infarcted myocardium and, possibly, cardiac valve replacement.

Whole-organ engineering of the kidney is particularly difficult because of its structural complexity and of the morphological and functional heterogeneity of renal cell types. As for other organs, research is currently focused on:--the matrix to support recellularization: synthetic, biodegradable or biological. Use of the extracellular matrix as a biological scaffold is the most promising approach. Rodent, porcine and rhesus monkey kidneys have been decellularized to obtain scaffolds with a preserved extracellular matrix and vasculature.--The source of cells for recellularization: embryonic stem cells, fetal cells, adult-derived stem cells, progenitor cells and adult-derived inducible, pluripotent stem cells have all been used. Nephron development results from mutual inducive interactions between the urethral bud and the metanephric mesenchyme, a process that can be reproduced in vitro. Ex-vivo "fabrication" of a kidney that could be implanted with no risk of rejection in patients with chronic renal failure appears ultimately feasible. Another area of research is the use of renal assistance devices--the bioartificial kidney--based on a bioreactor containing renal epithelial cells derived from tubules that maintain their reabsorptive, metabolic and endocrine functions. Phase II clinical trials have given encouraging results.

Hepatocyte transplantation has not yet reached therapeutic status, as it has proven difficult to transplant a sufficient number of functional hepatocytes able to integrate and proliferate inside liver plates. It has recently been shown that whole livers can be decellularized by portal infusion of detergents, yielding a decellularized scaffold with a well preserved vascular network and specific liver matrix. Perfusion of different combinations of cells through the portal vein of these scaffolds results in reconstitution of a complete functional organ that can be transplanted in small animals. An auto-constructed human liver could be engineered from exogenous liver scaffolds seeded with various cell populations, including autologous cells derived from induced pluripotent stem cells. Auto-constructed livers might replace conventional liver grafts in future.