Systemic mastocytosis is a rare myeloproliferative-like disease, characterized by an abnormal proliferation of mast cells in various organs. Two types of clinical manifestations can be distinguished: those related to release of mast cell mediators release and those related to tumor proliferation involving different organs, these later defining systemic mastocytosis. Until recently, treatment was mainly symptomatic, without anti tumor effect. These last years, advances have been made in the understanding of the disease with the discovery of the presence, in a number of patients, of mutations of the c-kit oncogene, coding for the receptor of the major growth factor for mast cells. These mutations induce autophosphorylation of the c-kit receptor in the absence of its ligand, the Stem Cell Factor. Based on experiences acquired in the treatment of myeloproliferative disorders, evaluation of new therapeutics, such as cladribine or interferon-alpha, is in progress. Finally, it would be possible to design, in the very next future, new tyrosine kinase inhibitors targeting specifically the mutant forms of c-Kit found in patients suffering from systemic mastocytosis.

Neuroblastoma and its benign counterpart, ganglioneuroma, are pediatric neuroblastic tumors arising in the sympathetic nervous system from neural-crest cells. Neuroblastoma, the most common extra-cranial solid tumour during childhood, is unique for its broad spectrum of clinical virulence from spontaneous remission to rapid and fatal progression despite intensive multimodality therapy. To a large extent, outcome could be predicted by the stage of disease and the age at diagnosis. However, a number of molecular events in neuroblastoma tumors, accounting for the variability of outcome and response to therapy, have been identified over the past decades. Among these, MYCN amplification is the most relevant prognostic factor and was the first genetic marker, in paediatric oncology, to be included in clinical strategies as a guide for therapeutic decision. This has allowed the most suitable intensity of therapy to be delivered according to a risk-stratified strategy, from observation to megadose chemotherapy with stem cell transplantation. Recent advances in understanding the biology and genetics of neuroblastoma will ultimately allow to select poor-risk patients for appropriate future biologically based therapies.

Bone marrow transplantation (BMT) is based on destruction of the patient's bone marrow with rescue of haematopoietic stem cells from a donor. Chronic graft-vs-host disease (GVH) is the major complication post-BMT and mimics some autoimmune diseases, such as scleroderma, sicca syndrome, primary biliary cirrhosis and an increased prevalence of various autoantibodies. Other autoimmune-like manifestations have been reported as case reports or short series. The most common are myasthenia gravis, polymyositis, autoimmune cytopenias and Graves' disease or autoimmune hypothyroidism.

In the central nervous system, neuron generation continues throughout adulthood. This neurogenesis is involved in a continual adaptative process in relation with the environmental complexity. It decreases with age and is reduced in several types of experimental conditions mimicking stress, depression, addiction and neurodegenerative diseases. It may be enhanced after excitotoxic, ischemic or traumatic injuries suggesting a compensatory adaptative response. Available data on this new concept in the field of neurosciences and possible therapeutic relevance are reported.

Hematopoietic stem cells (HSC) have been widely used for autologous and allodeneic transplantation during decades, although little was known about their migration, survival, self-renewal and differentiation process. Their sorting by the CD34(+) marker they express at the cell surface in human has been challenged by the recent discovery of HSC in the CD34(-) compartment that may precede CD34(+) HSC in the differentiation process. Until recently, stem cells present in the bone marrow were thought to be specific for hematopoiesis. Some experiments including clinical trials showing the formation of various tissues, muscle, neural cells and hepatocytes for instance, after transplantation of medullar cells, have challenged this dogma. In fact, the proofs of such a transdifferentiation process by HSC are still missing and the observations may result from the differentiation of other mulipotent stem cells present in the bone marrow, such as mesenchymal stem cells and more primitive multipotent adult progenitor cells (MAPC) and side population (SP) cells.

Rescue therapies for relapsing/refractory primary central nervous system lymphoma (PCNSL) and intraocular lymphoma (IOL) remain a challenging problem for clinicians. In 2001, we published encouraging results for 22 patients treated at relapse with a CYVE regimen combining high doses of Ara-C (50 mg/m(2)/d in 12 hours infusion dl through d5; 2 g/m(2)/d d2 through d5) and VP16 (200 mg/m(2)/d d2 through d5), followed by intensive chemotherapy based on high doses of thiotepa (250 mg/m(2)/d d-9 through d-7), busulfan (10 mg/kg total dose d-6 through d-4) and cyclophosphamide (60 mg/kg/d, d-3 and d-2 with hematopoietic cell rescue at d0. Patients were enrolled onto the study for a relapse (n = 10; 2 IOL, 3 CSF, 5 brain lesion) or for a refractory disease (n = 12; 9 IOL, 3 brain lesion). CYVE rescue was not administered to patients with refractory IOL who had previously received high doses of methotrexate and Ara-C as part of their first-line treatment. Twenty patients received the intensive chemotherapy and hematopoietic cells rescue. We updated our results in March 2003. Seven patients had neurologic adverse events during the entire procedure. With a median follow up of 6.2 years, the median overall survival is 91 months, and the median survival after intensive chemotherapy has not been reached.

Innovative biotechnical progress over the past few years regards stem cells and therapeutic cloning, which open promising medical horizons for many presently incurable diseases. THE CURRENT DEBATE: The research work in France has been stalled because of the prohibitions listed in the so-called "bioethical" laws of 1994. The ongoing revision of these laws is based on a certain number of ethical questions and launches a disputable parlementary debate. Other than reproductive cloning and research on the embryo, the possibilities provided by stem cells and therapeutic cloning should be emphasized and the different positions advanced specified, showing an evolution in the laws in France. ABUSIVE LEGISLATIVE PROHIBITIONS: The proposed law, which maintains the prohibition for research on the embryo, with a 5-Year dispensation, and which explicitly prohibits therapeutic cloning, is not in keeping with the widening of in this field expected by research teams. Many scientists and physicians, supported by patients' associations, are aware of the importance of therapeutic progress attached to such research. They should not be stalled in their studies by the prohibitions maintained in the new law.

Autologuous stem cell transplantation within regional infarcted or ischemic myocardium is currently a focus of experimental research world-wide, and could provide a unique way to ensure myocardial functional recovery. In order to benefit from immediate access to bone marrow stromal cells at the time of myocardial injury, and thus avoid the delay rendered necessary by autologuous harvesting and clonal expansion, the use of allogeneic stem cell could be of major interest. This experimental work is based on a unique mini-swine model in which the histocompatibility antigens are known, and perfectly controlled, through inbreeding and investigate the survival and the induction of an immune tolerance to allogeneic stem cells injected into the infarcted myocardium with the use of transient immunosuppression (12 days).

Up to now, there is no therapy in order to stimulate a remyelination in the adult central nervous system. So, the study the ontogenesis of oligodendrocytes at the cellular and molecular level could provide cues in order to design such a treatment that will be efficient to remyelinate patients after a multiple sclerosis relapse. In our work, we demonstrated that both neurotransmitters acting trough ionotropic receptors, expressed by oligodendrocytes precursors and some members of the neuregulin growth factors family, could modulate the proliferation and the differentiation of oligodendrocytes progenitors. Furthermore, we demonstrated that the graft of neural stem cells in experimental demyelinated lesion in adult animals is responsible for an efficient remyelination.

For several years, in Parkinson's disease patients, immature neuroblasts grafts could be realized. Those immature cells come from mesencephalic regions of six to ten weeks-old embryos. Given several technical problems, clinical outcome of the patients is not favourable and moreover, it appears that the cell source is very limited. That's the reason why the use of embryonic or somatic stem cells could be promising. Stem cells are able to self-renew, and could differentiate into several cell types. In this lecture, the author reviews the biological properties of different stem cells types in order to be used in cerebral graft in several neurological diseases. Given their recently unravelled phenotypic plasticity, somatic stem cells could be the best candidate for such a clinical use for autografts.

The ultimate objective of organ transplantation is to obtain a state of tolerance, i.e. long-term acceptance of the graft without immunosuppressive therapy in order to limit the complications of these treatments (viral infections, tumours, etc.). The various immunological mechanisms allowing a state of tolerance will be described in this review. Among these various experimental strategies, combined bone marrow (or haematopoietic stem cell) transplantation and organ transplantation, made possible by the development of non-myeloablative or less intensive conditioning, appears to be one of the most promising lines of research. This approach leads to colonization of the recipient by donor cells. This state is described as "macro-chimerism" and achieves a real state of central tolerance in relation to an organ derived from the bone marrow donor. We have shown recently that intravenous injection of apoptotic cells in combination with allogeneic bone marrow cells increases the success rate of bone marrow transplantation. In a model of combined bone marrow/solid organ transplantation, these apoptotic cells induce tolerance limited to the donor's bone marrow cell antigens without inducing auto-immunization. We therefore propose a new approach to cell-based therapy (using the immunomodulating properties of apoptotic cells) to promote the success of haematopoietic stem cell transplantation. This approach can be particularly useful in combined haematopoietic stem cell and organ transplantation in order to induce a state of macro-chimerism.

Aortitis consists in aortic wall inflammation from infectious or non infectious cause. It may lead to aortic aneurysm with a risk of rupture, which is life-threatening and may justify surgical procedures. The cause of the aortitis is sometimes obscure.

One of the negative aspects of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) is the increased risk of multiple pregnancies. There is an epidemic of twin pregnancies with a higher risk of obstetric, perinatal and neonatal complications than singleton pregnancies and with an important psychosocial, economic and financial impact for the parents to be. A reduction in the number of twins can only be obtained by the transfer of one embryo. Single embryo transfer with an acceptable pregnancy rate might be considered if a top quality embryo is available. The need to characterize embryos with optimal implantation potential is obvious. A top quality embryo is characterized by the presence of 4 or 5 blastomeres at day 2 and at least 7 blastomeres on day 3 after insemination, the absence of multinucleated blastomeres and<20% cellular fragments on day 2 and day 3 after fertilization. Others prognostic factors of implantation are discussed in this review. Judicious application of eSET can halve the twinning rate while maintaining the overall pregnancy rate.