Pluripotent murine embryonic stem (ES) cells can differentiate into all cell types both in vivo and in vitro. Based on their capability to proliferate and differentiate, these ES cells appear as a very promising tool for cell therapy. The understanding of the molecular mechanisms underlying the neural differentiation of the ES cells is a pre-requisite for selecting adequately the cells and conditions which will be able to correctly repair damaged brain and restore altered cognitive functions. Different methods allow obtaining neural cells from ES cells. Most of the techniques differentiate ES cells by treating embryoid bodies in order to keep an embryonic organization. More recent techniques, based on conditioned media, induce a direct differentiation of ES cells into neural cells, without going through the step of embryonic bodies. Beyond the fact that these techniques allow obtaining large numbers of neural precursors and more differentiated neural cells, these approaches also provide valuable information on the process of differentiation of ES cells into neural cells. Indeed, sequential studies of this process of differentiation have revealed that globally ES cells differentiating into neural cells in vitro recapitulate the molecular events governing the in vivo differentiation of neural cells. Altogether these data suggest that murine ES cells remain a highly valuable tool to obtain large amounts of precursor and differentiated neural cells as well as to get a better understanding of the mechanisms of neural differentiation, prior to a potential move towards the use of human ES cells in therapy.

Polycythemia vera is a myeloproliferative syndrome. This clonal disorder involves a pluripotent stem cell capable of differentiating into red blood cells, granulocytes, and platelets. Polycythemia vera is characterized by the overproduction of mature red blood cells in the bone marrow. Myeloid and megakaryocytic elements are also often increased. Polycythemia vera (PV) is rarely associated with pregnancy. About 20 cases have been reported. Prognosis of PV is not influenced by pregnancy. Conversely, pregnancy outcome is poor, due to the occurrence of gestational hypertension, stillbirth and induced prematurity. During pregnancy, clinical management needs to be close including a collaborative approach between obstetricians, hematologists and anesthesists. The risk of poor outcome may be reduced by the association of antiaggregant and anticoagulant therapy. Phlebotomy can be provided in order to maintain hemoglobin level under 42%.

Stem cell therapy of skeletal tissues involves the transplantation of stem cells to the tissues that have been damaged by injury or disease. Although these cells can be derived from embryos, the preferred source of skeletal stem cells is the bone marrow as it contains adult stem cells that can be easily driven towards a bone phenotype. More recently, cells with similar potentialities have also been derived from adipose tissue, muscle, or blood. A biomaterial (ceramics or polymers) is often required as a scaffold to promote cell adhesion, proliferation and differentiation as well as encourage vascular invasion and ultimately new bone formation. The first clinical studies are encouraging and suggests that stem cell therapy could be a prime method for bone reconstruction.

Leukemias are a group of malignant diseases caused by immature hematopoietic cells proliferating in the blood marrow. Some manifestations result from ocular-orbital involvement, which usually occurs through the central nervous system. Other manifestations stem from vasculopathy and/or hemorheologic disorders (anemia, thrombocytopenia, hyperviscosity).

Regarding cardiac failure, the year 2004 was notable for the dissemination of indications for the use of medical devices in heart failure: indications for cardioversion with the long awaited publication of the COMPANION study, advancement of the concept of intra-ventricular asynchronism, and studies of defibrillators in non-ischaemic cardiac failure (COMPANION, DEFINITE, SCD-HeFT, TOVA). Furthermore, pragmatic clinical studies allowed refinement of the uses of BNP (diagnostic and prognostic), underlining the importance of renal function and its progression during hospitalisation, and the risks of using strong, modern therapy in populations without "ad hoc" surveillance which do not correspond with study populations (aldactone in Canada). Just as in coronary patients, it appears to be important to commence full medical treatment prior to hospital discharge, because treatment is rarely changed thereafter. The management of seriously ill patients is evolving with several therapeutic advances: the methods of selecting patients for heart transplants have changed, with the advancement of opportunities for circulatory assistance. Attention has also been turned to the significant group, still poorly understood, of patients with diastolic heart failure, for whom diagnostic methods have been defined, as well as their clinical characteristics. Lastly the medication studies: new drugs in acute cardiac failure (preliminary results for vasopressin antagonists), wider indications for betablockers in elderly subjects (SENIORS), and advances in cellular cardiomyoplasty (using haemopoietic stem cells especially this year). It has been a fruitful year, difficult to summarise in a few lines, or even several pages....

Bone regeneration is only possible if stem cells give rise to progenitors of osteoblasts, chondroblasts or chondroidocytes. Stem cells and osteogenic progenitors were evidenced in bone marrow while only progenitors can be found in periosteum. Bone marrow stem cells did show an amazing plasticity and some cells of the bone surrounding tissues such as perivascular cells, adipocytes, muscle cells or even circulating cells are able to transdifferentiate in osteoblasts when submitted to an osteogenic environment. We have shown that the destruction of both bone marrow and periost impairs the bone healing. It indicates that the periost and bone marrow destruction removes the predetermined osteogenic cells and the informative factors able to induce the transdifferenciation of the cells contained in the peri-osseous tissues.

The ontogenesis of hematopoiesis is classically described as a series of successive steps: the first takes in the yolk sac where blood islands differentiate. Then, cells deriving from these structures migrate and populate the transient hematopoietic organs such as the liver and the spleen. At last, the eventual migration allows the establishment of bone marrow hematopoiesis. This theory described in almost all the textbooks of Human Embryology does not fit with recent experimental data. Indeed, the construction of quail-chick chimeras shows that the yolk sac does not contribute to the adult hematopoiesis in birds. Adult hematopoietic cells arise from a population located on the ventral side of the aorta both in birds and mammals. The aortic population derives from the para-aortic splanchnopleura and its derivative, the so-called AGM (Aorta-Gonad-Mesonephros). These new data provide new concepts to understand the process of ontogenesis of the hematopoietic system in vertebrates.

Severe ocular burns are potentially blinding injuries. During the first month, ocular surface destruction is caused by a vicious circle of complications that may result in the pathological state of total limbal stem-cell deficiency. Amniotic membrane transplantation can be considered an early, if not immediate, surgical procedure to promote epithelialization and calm inflammation so that scarring-induced sequelae can be prevented in the chronic stage. However, when partial or total limbal stem-cell deficiency involves one or both eyes, corneal surface reconstruction relies on transplantation of autologous limbal stem cells, an allogenic source of limbal stem cells or corneal epithelial stem-cell transplantation. In this late stage, amniotic-membrane transplantation may improve prognosis of keratolimbal allograft and is useful in the treatment of symblepharons.

Eye burns are frequent among eye traumas. They induce different effects on the ocular structures, depending on the type of burn: chemical, with an important difference between acids and bases, thermal, or ionizing rays. The physiopathology of eye burns reflects the different stages of progression, with a first stage of destruction, a second stage of cleaning and inflammation, and a last stage of reconstruction and scarring. The final prognosis depends on the initial lesions, not only involving the eye ball, but also the conjunctiva and eyelids. Chemical burns by basic fluids have the worst prognosis because they are able to penetrate the tissues quickly. Burns by acids have a better prognosis and thermal burns are located only at the injured area. Treatment is most effective at the initial stage of destruction and can dramatically change the prognosis. The secondary phase of cleaning includes the entire biochemical cascade of inflammation and the production of proteases. At this stage, treatment can be effective but must be closely monitored because it can inhibit progression to the last stage of scarring. At the scarring stage, neovascularization begins, induced by initial ischemia, the reconstruction of epithelium with a probable role of stem cells, the reconstruction of nerve fibers depending on the nerve growth factor (NGF), and the reconstruction of extracellular matrix in which matrix metalloproteinases (MMPs) are essential. At this stage, therapy can only be surgery of functional after effects and esthetic anomalies.

In several trials, the GnRH antagonists regimens have been associated with a slightly lower pregnancy and implantation rate than the established GnRH agonist protocols. Several embryo classification systems have been developed to grade embryo quality, and a cumulative embryo score has been proposed to predict pregnancy. The cumulative embryo score is based on a 4-point embryo score in which all cleaved embryos were assigned 1 point and 1 additional point was added for each of the following features: absence of fragmentation (or fragmentation involving <20% of the embryonic surface), absence of irregularities in blastomere size or shape, and four-cell stage (regardless of cell morphology). This cumulative embryo score is highly correlated with embryo implantation rates. In a non prospective study concerning 641 IVF cycles with oocyte retrieval, pregnancy and implantation rates were statistically lower in the group of patients treated with GnRH antagonist. The explanation of this difference is the indication in IVF cycles: the women with tubal infertility and/or endometriosis had lower pregnancy and implantation rates in IVF cycles if an antagonist was administrated. There was no difference between the 2 groups in ICSI cycles. Subsequently, in IVF cycles, antagonist should not be administrated to women with tubal infertility and/or endometriosis.

Cancer represents a major problem of public health. New therapeutic approaches are needed to complete the present strategies. The use of immunotherapy for cancer treatment is a promising strategy. Allogeneic stem cell transplantation (allo-SCT) is the most widely used form of immunotherapy. The allogeneic immune effectors infused with the graft can recognize and eradicate the patients' tumoral cells.

Fronto-temporal dementias (FTD) were described a century ago on the macroscopic basis of frontal and/or temporal lobe atrophy. Progress in neuropathology, immunohistochemistry, biochemistry and genetics has since shown that they are heterogeneous entities, encompassing many different diseases with similar clinical presentations. A few, such as tauopathies due to mutations of the gene coding for tau protein (MAPtau form a well-defined group. Definition and grouping of other types of FTD is still problematic.

Since the early sixties, many concepts concerning neurogenesis have been progressively ruled out. Proof of the persistence of a physiological neurogenesis in adult mammals, including humans, raised the concept of a unique precursor cell giving birth to neurons and glial cells. According to this concept, a real continuum between neuroepithelial cells, radial glia and astrocytes exists from the embryonic period to adult age and generates both neurons and glial cells. Different factors, either secreted in situ or transported by blood, can influence this physiological neurogenesis process. The targets and role of newborn neurons are not clearly understood. In pathological conditions (ischemia, epilepsy, lesions), the physiological neurogenesis process is enhanced; however the significance of this neurogenesis excess (beneficial or deleterious) is not completely known. Advances in understanding the regulation of neurogenesis in these different conditions represent hopes of new therapeutic procedures, not only by improving the control of differentiation and survival of transplanted stem cells, but also by the possibility of modifying the processes of "endogenous neurogenesis".

The role of the renin-angiotensin system was previously thought to be restricted to the cardiovascular system. It now appears that this system also plays an important role during development, and especially in hematopoiesis. The different elements of the renin-angiotensin system are expressed early during embryogenesis. The renin system plays a role at different steps of hematopoiesis, notably during the first wave of hematopoiesis in the chick embryo system (primitive hematopoiesis), and during the adult phase of hematopoiesis in the fetus (definitive hematopoiesis). In addition, this system is involved in hematopoiesis following experimental irradiation of mice: renin system antagonists improve hematopoiesis in this situation.