The pattern of autoimmune hemolytic anemia has changed significantly these last 15 years. With regard to the diagnosis strategy, the use of gel filtration technique to perform the direct antiglobulin test (DAT) has decreased the number of autoimmune haemolytic anemias with negative tests results. In recent years, autoimmune haemolytic anemia increased in patients receiving purine nucleoside analogues, blood transfusions, solid organ transplantation or hematopoietic stem cells transplantation. These difficult autoimmune haemolytic anemia cases need to use new kinds of treatments. With regard to the treatment, very little progress was made this latter 50 years. The discovery of the efficacy of anti-CD20 antibody in this disease represents a breakthrough. Nowdays, the second-line treatment includes rituximab or splenectomy. Sometimes, the anti-CD20 treatment could be proposed in first-line but some clinical trials are needed.

Allogeneic hematopoietic stem cell transplantation is the most widely used form of immunotherapy. The allogeneic immune effectors infused with the graft can recognize and eradicate the patients' tumoral cells. The curative potential of allogeneic hematopoietic stem cell transplantation is classically based on two mechanisms: the conditioning myelo-ablative or immunosuppressive inducing either the cytoreduction of tumoral cells or tolerance and the immune control mediated by allogeneic immune effectors (graft-versus-leukemia or tumor effect, GVL or GVT). Allogeneic hematopoietic stem cell transplantation is currently under important mutations because of better understanding of the GVT mechanisms and the development of new treatment techniques with: (a) allo-hematopoietic stem cell transplantation of peripheral blood stem cells after mobilization with G-CSF and allotransplant of cord blood cells; (b) increase number of allogeneic hematopoietic stem cell transplantation from unrelated and haplo-identical donors; (c) immunomodulation according to the chimerism and residual disease documentation with donor lymphocyte infusion (DLI); (d) development of reduced intensity conditioning regimens aiming to reduce the toxicity while favoring the immune component of the anti-tumoral effect; (e) development of sequential chemotherapy followed by allogeneic hematopoietic stem cell transplantation after reduced intensity conditioning in case of refractory diseases. In addition the present experience shows clearly that the allogeneic hematopoietic stem cell transplantation strategy should be developed and refined because of the potential benefit that can be expected in some patients' sub-groups and then allogeneic hematopoietic stem cell transplantation, real immunotherapy should be included in the global therapeutic strategy in onco-hematology.

BK virus (BKV) belongs to the Polyomaviridae family. It is widespread in adults. Primary infection typically occurs during childhood, without specific symptoms, followed by a state of non-replicative infection in various tissues, with the urogenital tract as the principal site. Immunosuppression promotes reactivation and replication of BKV. After kidney allograft, active infections can cause interstitial nephritis up to graft loss. In hematopoietic stem cell transplant (HSCT) recipients,BKVinfections are associated with hemorrhagic cystitis (HC). The pathogenesis of HC after HSCT represents an interplay between urotoxicity of the conditioning regimen, BKV infection and alloimmune reactions from donor lymphocytes targeting the recipient uroepithelial cells. The diagnosis is based on the quantification of BKV DNA by PCR in urine and blood. The current standard of care for HC is symptomatic, since to date no antiviral drug with proven efficacy against BKV replication has been licensed.

Stem cells are a non-coherent group of cells that have little in common. Despite the fact that these diverse cell types are regarded as belonging to the same category, they do not share molecular markers. The definition of stemness is therefore descriptive, relating to potentials of the cells rather than to the actual properties that they harbor. This situation is confusing and causes unnecessary debates in this field of research. It is therefore of paramount importance to find a new, molecular definition of stemness, that would consist of the cellular machineries which constitute the stem cell state.

Mesenchymal stem cells (or stromal cells) have been initially characterized in bone marrow, but since, they have been identified in almost every tissue. Their multiple properties, namely differentiative capacity, production of cytokines and trophic molecules, and their immunosuppressive potential undoubtedly offer many therapeutic advantages, both for regenerative medecine or to relieve immune or inflammatory diseases. This is illustrated by the high number (> 100) of ongoing clinical trials with these cells. However, a prerequsite for their safe use in clinics is to guarantee that their production meet the good manufacturing practices, and that the final product is validated by adequate controls. It is thus quite a challenge to move from procedures defined for a research use to large scale production that fits with the national and international rules in terms of standardisation and controls. This underlines the importance of developping interacting networks between research teams, physicians and the industrial R&D departments. This fruitful collaboration will ensure the definition of appropriate and safe procedures for a successful therapeutic application.

Tissue damages or loss of organs often result in structural and metabolic changes that can cause serious complications. The therapeutic objective of tissue engineering (TE) is to recreate, regenerate or restore function of damaged tissue. TE is based on the coalescence of three components: a scaffold or matrix from natural or synthetic origin biodegradable or not, reparative cells and signals (hypoxia, mechanical stress, morphogens…). Articular cartilage, bone and blood vessels are tissues for which TE has progressed significantly, from basic research to clinical trials. If biomaterials must exhibit different properties depending on the tissue to regenerate, the cellular component of TE is mostly represented by stem cells notably adult mesenchymal stem cells harvested from bone marrow or adipose tissue. In recent years, progress has been made in our understanding of the biological mechanisms that govern stem cell differentiation and in the development of materials with controlled physicochemical and biological properties. However, many technological barriers and regulations concerns have to be overcome before tissue engineering enters into the therapeutic arsenal of regenerative medicine. This review aims at highlighting the progress in the use of stem cells for engineering osteoarticular and vascular tissues.

Mesenchymal stem cells (MSC) have attracted recent attention for their cell therapy potential, based in particular on their immunosuppressive properties, which have served as the basis for the treatment of autoimmune diseases. Interestingly, MSC have been used in cell therapy strategies to deliver therapeutical genes. Cell therapy approaches taking advantages of MSC have been proposed, as MSC display a potential tropsim for tumors. However, all these strategies raise a series of questions about the safety of MSC, as MSC could enhance tumor growth and metastasis. This review summarizes recent findngs about MSC in carcinogenesis.

Mesenchymal stem cells/multipotent marrow stromal cells (MSC) have the ability to participate in there construction of tissues both directly by providing repair cells (essentially those originating from mesoderm)and indirectly by modulating inflammatory and immune responses. This wide range of properties makes these cells very appealing to treat various pathological conditions. They have been first used in 1995 as supportive cells to facilitate hematopoietic stem cells engraftment, and then to minimize the deleterious consequences of graft versus host disease by their immunosuppressive function. Their robust osteogenic differentiation capacity has also been evaluated in numerous preclinical settings of healing/repair but more rarely in human clinical trials. During the past 10-15 years, the potential benefit of their paracrine actions has been tested in various situations such as to facilitate repair after cutaneous defects after burns or lower consequences of ischemic strokes. The purpose of this series of short texts is not to give an exhaustive panorama, but to discuss some well-identified indications in four different fields : auto-immune diseases,bone repair, vascular regeneration and eye lesions such as corneal and retinal defects.

Since their efficiency to treat graft versus host disease has been proven, mesenchymal stem cells (MSC) represent a promising cell therapy approach for the treatment of immune disorders. In this context, much attention has focused on their mechanisms of action, in particular once the fact that their immune properties are also crucial for their efficiency in regenerative medicine was demonstrated. By their production of various and redundant soluble factors, MSC exert powerful anti-inflammatory and immunosuppressive effects targeting the main immune cell subsets. These immunoregulatory properties are essentially inducible by inflammatory mediators. In addition, it is now clear that allogeneic MSC are not immunoprivileged in immunocompetent recipient in agreement with their low persistence in vivo. They should thus display an early "touch-and-go" effect involving both direct interactions with recruited immune effectors and further amplification of this immunosuppression process through activation or conditioning of other regulatory immune cells. A better understanding of immunological properties of MSC will clearly improve their use in clinical settings.

This brief overview summarises the main characteristics of bone marrow mesenchymal stem cells and of adipose-derived stem cells: methods of obtention, phenotype, differentiation potential, hematopoiesis-supportive (stromal) capacity, and immunosuppressive properties. Two points are discussed in detail: 1) criteria for stemness: multipotency, self-renewal, plasticity, and 2) the repair mechanisms implicated in the different indications of cell therapy using these cells: reconstitution of the tissue functional compartment by repopulation consequent to proliferation and differentiation or reprogrammation, stromal effects by secretion of angiogenic, anti-apoptotic, anti-fibrogenic factors, molecules involved in the regulation of inflammation, etc.

Recent progresses have changed the paradigms for the treatment of MDS. Careful patient screening and prognostic stratification using IPSS score is necessary before any treatment decision. For lower-risk MDS where anemia is the major problem, treatment with ESA should be considered first. In patients who require red blood cells transfusions, iron overload must be monitored carefully in order to consider iron chelation therapy. A new drug such as lenalidomide which is active in MDS with del5q is currently under investigation in non-del5q MDS. For patients with higher-risk MDS, AML transformation is the major issue. Therefore aggressive treatment approaches such as allogeneic HSC transplant or intensive chemotherapy can be offered to selected subsets of patients. However, for the vast majority, demethylating agents and namely 5-azacytidine currently represent the standard of care. Patient information and participation in clinical trails are important aspects of the current management of MDS.

Myeloproliferative/myelodysplastic syndromes are rare diseases that include a proliferative component, mainly on the white cells and platelets, and a dysplastic component that accounts for one or several cytopenias. The most frequent of these diseases in chronic myelo-monocytic leukemia, a disease of elderly people that has long been associated with myelodysplastic syndromes in biological studies as well as in clinical trials. The recent identification of a number of genetic mutations in the leukemic clone, including frequent mutations in TET2, ASXL1 and RUNX1, less frequent mutations in NRAS, KRAS and C-CBL, and rare mutations in JAK2, FLT3, IDH1, IDH2, and EZHR2 may improve our understanding of the pathogenesis of this disease. Patient care depends on the disease risk, especially the percentage of blast cells in the bone marrow, the age and the performance status. Supportive care is required in all patients. In high risk patients, the only curative therapeutic is allogeneic hematopoietic stem cell transplantation, which is rarely feasible due to the age of the patients and the absence of donor. Demethylating agents such as azacitidine and decitabine are currently the most efficient drugs. The prognosis remains poor, with a median survival lower than 24 months.

Adipose tissue is abundant and well known for its involvement in obesity and associated metabolic disorders. Its uses in regenerative medicine recently attracted many investigators, as large amounts of this tissue can be easily obtained using liposuction and it contains several populations of immature cells. The largest pool of such cells corresponds to immature stromal cells, called adipose-derived stromal cells (ADSCs). These cells are purified after proteolytic digestion of adipose tissue and selection by an adherent step. ADSCs display many common features with mesenchymal stem cells derived from bone marrow, including paracrine activity, but with some specific features, among which a greater angiogenic potential. This potential is now investigating at clinical level to treat critical ischemic hindlimb by autologous cells. Other potentials are also investigated and the treatment of fistula associated or not with Crohn's disease is reaching now phase III level.

The methods used to collect hematopoietic stem cells in their natural environment (bone marrow or cord blood) or in the peripheral blood after stimulation are well-defined and ruled both to ensure the donor security and perform a quality hematopoietic transplantation. Safety of the familial or non-familial donor must be ensured not only during the collection but also on a medium- or a long-term basis. The stem cells amount in a graft and its characterisation depend on the collection site of hematopoietic stem cells and on the technique used. The knowledge of conditions influencing these amounts allows optimising the hematopoietic stem cells collection while preventing conditions in which the donor safety could be decreased. The collection site also influences the collection of significant amounts of other blood cells. This knowledge conditions the preparation procedures of the graft in cell therapy units or the management of per- or post-transplantations complications in haematology units. Thus, hematopoietic transplantations concern not only hematological units but also the teams involved in various stages of donor selection, hematopoietic stem cells collection and graft preparation. In order to allow an appropriate care of both donor and recipient, a concomitant knowledge of all the stages involved in hematopoietic collection conditions, characterisation of collected cells, hematological diseases and conditioning must be brought to hematological, collection and cell therapy teams.

Mesenchymal stromal cells are defined as non-hematopoietic progenitors characterised by their adherence to plastic in culture, their expression of non-specific markers and their differentiation potential into cells of mesodermic lineage. Resident in numerous tissues, mesenchymal stromal cells are now available from several sources, including both adult and foetal tissues. After their administration, mesenchymal stromal cells preferentially migrate to injured tissues. Mesenchymal stromal cells have therapeutic effects in numerous animal models of tissue injury by a mechanism not yet clearly understood. Mechanisms likely involved in repair can be the production of paracrine, anti-inflammatory and anti-apoptotic factors, as well as cell replacement by their differentiation potential. Mesenchymal stromal cells possess immunosuppressive properties on both innate and adaptative immunity in vitro and in animal models of autoimmunity. Currently their immunosuppressive properties allow testing of mesenchymal stromal cells in allogenic context, although this use requires further investigations. Mesenchymal stromal cells can be isolated and expanded in vitro in clinical grade conditions. They represent a promising candidate for the cellular therapy of diseases, such as acute myocardial infarction, diabetes, graft versus host disease or neurodegenerative diseases. Critical points including the standardization of production and long term toxicity have to be resolved before their large scale use in clinical conditions.

We report the case of a voluminous tumor of the adrenal diagnosed in a young pregnant woman at 26(th) week of amenorrhea. Morphologically, a soft white tumor with haemorragic areas was observed, made of sheets of monomorphous, medium sized, spindle-shaped to polygonal, with high mitotic activity. Tumorous cells expressed cytokeratins AE1/AE3, EMA, and CD99 (expression of vimentin is not relevant). Contemplated diagnoses included poorly differentiated synovialosarcoma, sarcomatoid carcinoma and Ewing tumor. Thanks to molecular biology, showing the specific transcript of Ewing/peripheral primitive neuroectodermal tumor (pPNET) EWS/FLI1, the diagnosis of this atypical tumor in an unusual location was performed. Indeed, 75% of Ewing tumors involve bones (especially, the diaphysis of long bones) and 20 to 25% soft tissues. Primitive visceral involvement is rare; less than 10 cases of adrenal involvement have been reported. The hypothesis that Ewing cell's origin is a mesenchymal stem cell, which may derive from neural crest cell, could explain the uncommon adrenal involvement. Diagnosis of Ewing tumor is based on pathologic and molecular findings, especially in atypical cases.

Numerous clinical and experimental studies have been performed on endothelial progenitor cells since their discovery in 1997. However, the lack of consensus on both their definition and study method is confusing. The purpose of this review is to describe the usual in vitro protocols, and the links with chronic renal insufficiency.

The incidence of chronic kidney disease leading to end-stage renal disease has significantly increased and may reach epidemic proportions over the next decade. Regardless of the initial insult, the progression of most forms of renal disease results in tubulo-interstitial fibrosis. This has been closely correlated to the future appearance of renal failure and has therefore been associated with poor long-term prognosis. New molecules and agents to limit the development of tubulo-interstitial fibrosis and slow down the progression towards end-stage renal disease are needed. In the past twenty years, many efforts have been made to understand the mechanisms of tubulo-intersititial fibrosis with the final goal to develop new therapeutic strategies. In this context, this review will focus on the mechanisms and factors involved in the development and the progression of renal fibrosis and will discuss the new promising therapeutic strategies in animal and humans.