The use of lipostructure to treat burn sequelae is more and more common today. The regeneration capacities of mesenchymal stem cells appear promising on this sequelae skin, which is poorly vascularized, retractile and often painful. The aim of our study is to establish the analgesic properties, and the functional and aesthetic improvements gained by using lipostructure to treat burn sequelae. Forty-three patients who received lipostructure for burn sequelae according to the Coleman method between 2005 and 2017 were selected. Results regarding aesthetic, analgesic and mobility gain were recorded, with a minimum follow-up of one year postoperatively. Our patients consisted of 32 women and 11 men, with a mean age of 31.7 years (15 to 64 years). The mean follow-up during the study was 49.8 months (2 to 205 months). Patients received an average of 1.3 (1 to 3) sessions of lipostructure with an average of 153 cc (10 to 1040 cc) per session. Sequela sites were the face for 13 patients, the upper limb for 13 patients, the lower limb for 16 patients and the trunk for 4 patients. Twelve patients had lesions on multiple locations. Twenty patients benefited from this surgery for purely aesthetic or functional reasons, and 23 for painful sequelae. A significantly lower EVA was observed after surgery and a functional gain thanks to the restoration of no longer painful amplitudes. An aesthetic gain was also reported in more than three quarters of cases. In two cases, the analgesic effect decreased after one year and required a second lipostructure. The use of lipostructure in burn sequelae has already proved its efficiency with regard to the functional aspect, aesthetics and also analgesia. However, the evaluation of results is based on scales that are still imperfect. Lipostructure is not the only type of surgery used in burn sequelae. Local plasty or skin grafts are also used, but they are more invasive and have no direct analgesic effect. Lipostructure is only possible on mature, soft and non-adherent scars in order not to traumatize adipose cells. Post-burn skin is defined by retractions and adhesions to deep planes, requiring heavy rehabilitation work beforehand. Finally, the effect is not always sustainable and the duration of efficiency remains unknown. Lipostructure has its place in the treatment of hyperalgic and unsightly burn sequelae that are responsible for a functional and social disability in the patient.

For more than a decade, the existence of ovarian stem cells that can contribute to neo-oogenesis in the adult ovary is reported by some teams, challenging the dogma according to which mammalian females are born with a fixed and non-renewed germinal cell pool. The presence of germinal stem cells with mitotic activity suggests the possibility of potential postnatal oogenesis. These cells have both germ-line and stem cell markers in culture. They have been isolated using different strategies and their ability to differentiate into oocytes has been demonstrated since after reintroduction in an ovarian somatic environment, these cells generate follicles capable of producing healthy offspring in rodents. However, many scientists remain skeptical and question the reliability of the methods used. Despite that there is no consensus on the origin of these ovarian stem cells, private companies are now proposing to use their stem cell potential to treat human infertility.

Careful sequencing studies on small samples of normal oesophageal epithelium reveal the presence of very abundant cellular clones harbouring mutations in known cancer genes (and elsewhere). The number and size of these clones increases with age. This surprising finding confirms previous studies on sun-exposed epidermis. It has important implications for the understanding of cancer initiation and will hopefully lead to conceptual and clinical advances.

Therapeutic progress in primary cutaneous lymphomas continues to be largely dominated by the T-cell lymphomas, towards which the great majority of recent therapeutic innovations have been directed. The latter include local treatments consisting either of relatively classical but "revamped" approaches involving different pharmaceutical forms (example: chlormethine gel) or else lower but seemingly equally effective dosages (electron therapy), or of more innovative approaches (example: UVA-1, dynamic phototherapy, imiquimod, resimiquimod). However, significant progress has been made chiefly in terms of systemic treatments with the emergence of "targeted" drugs that directly and specifically target tumour cells (monoclonal antibodies directed against CD30, CCR4 or CD158k) and the further development of "small" molecules such as histone deacetylase inhibitors and new cytostatics. Immunotherapies, which have proven so effective in other areas of oncodermatology, are also of great interest, while allogeneic haematopoietic stem-cell transplantation has clearly shown its superiority over autologous transplantation and now constitutes a significant component of the therapeutic arsenal in advanced disease. While the innovations in terms of B-cell lymphomas are certainly less significant, mention must also be made of the value of rituximab combined with polychemotherapy (CHOP) and of lenalidomide (as second-line therapy) in primary cutaneous diffuse large B-cell lymphoma, leg type, along with the development of localized (very) low-dose radiotherapy in unilesional or paucilesional indolent forms.

The prognosis for acute lymphoblastic leukemia (ALL) in adults remains poor in refractory or relapsed (R/R) situations. Among the immunotherapy strategies that have recently been developed, CAR-T cells (chimeric antigen receptor modified T-cells) represent a major technological and therapeutic advance in the management of adult and pediatric patients with such resistant diseases. The first CAR-T trials targeting the ubiquitous B-cell antigen CD19 showed very encouraging results with complete remission rates of approximately 80%. Cytokine release syndrome (CRS) and neurotoxicity are two major and potentially life-threatening adverse events, that require coordinated management with intensive care units and graduated use of IL-6 pathway blocking antibodies and steroids. In addition to immediate toxicity, many clinical issues arise such as ALL treatment from apheresis to CAR-T infusion, the role of allogeneic hematopoietic stem cell transplant (HSCT) before or after CAR-T therapy, or the reduction of escape mechanisms mostly driven by the loss of target expression. The development of these strategies in other subtypes of acute leukemias, including myeloid acute leukemia, is confronted with the expression of antigenic targets by healthy tissues and the potential risk of prolonged cytopenias. This review adopts a clinical perspective to detail the main results of CD19 CAR-T in ALL and the challenges raised by this new therapeutic approach. Cet article fait partie du numéro supplément Les cellules CAR-T : une révolution thérapeutique ? réalisé avec le soutien institutionnel des partenaires Gilead : Kite et Celgene.

The recommendations of the French Health and Drug Safety Authorities (HAS/ANSM-Haute Autorité de santé/Agence nationale de sécurité du médicament) are known, but there are always new developments underway. With regards to CMV suppression, there is the introduction of platelet glycoprotein Ia and the Intercept (Amotosalem+UVA) inactivation method which addresses bacterial risk. The irradiation of platelets is included in the recommendations to ensure HEV-negative plasma post allograft. In terms of blood transfusion safety, these measures as well as the broader spectrum of Ia, particularly for arboviruses, are a real breakthrough. The survey conducted in clinical services and the services providing blood products for transfusion along with a literature review have shown that several improvements need to be made. The first is a reduction of transfusions of concentrated red blood cells with introduction at a threshold of 7g/dL during hospitalization of patients without a fragile clinical status. The second improvement would address transfusion of refractory thrombocytopenia, encouraging an increase in discussion between clinicians and those conducting the transfusion in order to consider different etiologies and to identify appropriate care protocols. Third would be the need for the transmission of information between the transplantation doctors and blood transfusion specialists in order to define an approach to transfusion care adapted to the patient's situation. It is important to inform and educate patients about transfusion protocols post allotransplant or autotransplant. It must be clearly communicated to patients that they should always have on their person their blood group documentation. This is especially true when receiving care for a hemopathy or an autologous transplant. If undergoing an allogeneic transplant, patients should also carry transfusion guidelines post autotransplant or post allotransplant along with the phone numbers for the stem cell transplantation department and the blood transfusion center responsible for their care.

The purpose of this article is to detail the major gastroenterology novelties for 2018. In the field of hepatology we address the monitoring of hepatocellular carcinoma, the Baveno VI extended criteria for the detection of oesophageal varices and the management of cramps in cirrhotic patients. Concerning intestinal inflammatory diseases, two novel treatments have recently been approved by the European Commission, including injection of stem cells for the treatment of complex perianal fistulas and the JAK inhibitor tofacitinib for the RCH (ulcerative colitis). Finally, we provide an update on the diagnostic criteria for eosinophilic esophagitis and a new therapy that's was recently validated for the treatment of primitive biliary cirrhosis.

Mesenchymal stromal or stem cells (MSCs) are multipotent adult cells that can be isolated from a variety of adult or neonatal tissues, such as bone marrow, fat tissue, placenta or umbilical cord. A therapy based on MSCs can be justified in osteoarthritis (OA) thanks to their differentiation abilities but mostly, to their paracrine and immunosuppressive properties. Possible therapeutic strategies therefore rely on the articular injection of MSCs suspensions for trophic activity or the implantation of MSCs combined with biodegradable materials for tissue engineering applications. Depending on the mode of administration and behavior after implantation, they can decrease local inflammation, prevent chondrocyte hypertrophy and apoptosis as well as differentiate into cartilage-forming chondrocytes. In this review, we summarize pathophysiological and mechanistic data and discuss perspectives confirming the interest of MSCs as a potential therapeutic strategy in OA.

Donor lymphocyte infusion (DLI) can be proposed to treat or prevent the relapse of malignant hemopathies following allogeneic stem cell transplantation. The efficiency has been mainly reported in the treatment of CML and low-grade lymphomas while the anti-tumoral activity is less in forms of acute leukemia and myelodysplastic syndromes. The GVL benefit should always be compared to the possible toxic effects of GVHD. This article updates the initial SFGM-TC recommendations, proposed in 2013, that were focused on the use of DLI. Doses of DLI in the context of haplo-identical stem cell transplantation are now indicated. We confirm that remaining mobilized stem cells may be used as classical DLI. The definition and the place of preemptive and prophylactic DLI are precisely given. Recommendations regarding the quality of thawed DLI as well as necessary clinical and biological follow-up are also described in detail.

The Francophone Society of Bone Marrow Transplantation and Cellular Therapy (SFGM-TC) organized the 8th allogeneic hematopoietic stem cell transplantation clinical practices harmonization workshop series in September 2017 in Lille, France. In this article we give the indications of autologous stem cell transplantation in multiple sclerosis as well as recommendations regarding post-transplant follow-up of patients under the hospice of the SFGM-TC and the Francophone Society of Multiple Sclerosis.

Since the derivation of the first pluripotent embryonic stem cell lines in mice in the early 1980s, a plethora of lines has been obtained from various mammalian species including rodents, lagomorphs and primates. These lines are distinguished by their molecular and functional characteristics and correspond to the different pluripotency states observed in the developing embryo between the "blastocyst" and "gastrula" stages. These cell lines are positioned along a gradient, or continuum of pluripotency, the ends of which are epitomized by the naïve and primed states, respectively. Conventional human pluripotent stem cells self-renew in the primed state of pluripotency (ie, at the bottom of the gradient), a position that is undoubtedly the cause of their natural instability. Recent studies aim to generate naive human pluripotent stem cells (at the top of the gradient). The importance of this research in the perspective of medical applications will be discussed.

Pediatric acute megakaryoblastic leukemia (AMKL) are generally associated with poor prognosis and the expression of fusion oncogenes involving transcriptional regulators. Recent results indicate that the ETO2-GLIS2 fusion, associated with 25-30 % of pediatric AMKL, binds and alters the activity of regulatory regions of gene expression, called "enhancers", resulting in the deregulation of GATA and ETS factors essential for the development of hematopoietic stem cells. An imbalance in GATA/ETS factor activity is also found in other AMKL subgroups. This review addresses the transcriptional bases of transformation in pediatric AMKL and therapeutic perspectives.

Cell therapy in heart failure: what's up? The routine practice of skin and bone marrow transplantation provides the best illustration that cells can have a therapeutic effect. Attempts have thus be made to exploit this effect for the treatment of heart failure with the initial objective of physically replacing dead cardiomyocytes by new exogenously-supplied cells even though there has been a recent paradigm shift whereby the primary mechanism of action is rather attributed to the cell-derived secretion of factors that would harness endogenous repair pathways. The first wave of clinical trials, which have used cells from various sources, have failed to convincingly demonstrate improved outcomes but these studies have generated data that should now be leveraged for optimizing the efficacy of the technique through the selection of the most functionally efficacious cells, their combination with biomaterials and the development of delivery modalities ensuring an improved initial retention of the cellular graft. Confirmation that the primary mechanism of action is paracrine signaling possible paves the way for an a-cellular cell therapy whereby only secretion products would be administered to the patient while the role of cells would be limited to their in vitro production.

The limbus is the anatomical and functional barrier between corneal and conjunctival epithelia. It is characterized by presence of the limbal stem cell niche which allows corneal homeostasis to be maintained. Limbal stem cell deficiency is characterized by a dual process: insufficient regeneration of corneal epithelium, which cannot therefore assure its function of physiological support, associated with corneal invasion by conjunctival proliferation. Diagnosis is currently made via routine clinical examination, corneal impression cytology and in vivo confocal microscopy (IVCM). Slit lamp examination shows abnormal limbal anatomy, thin and irregular epithelium with late fluorescein staining, and superficial vascularization. With its high resolution, IVCM allows identification of limbal and corneal epithelial changes at a cellular level in en face views, parallel to the corneal surface, but with a restricted viewing field of the corneal surface. It shows a poor transition between the corneal and conjunctival epithelia, associated with a loss of the normal corneal epithelial stratification, low basal cell and sub-basal nerve plexus densities, even with sub-epithelial fibrosis. Optical coherence tomography in central cornea and at the limbus, with scans in different orientations, allows a quick, global and non-invasive analysis of normal eyes and those with limbal stem cell deficiency. It shows a thin limbal epithelium, lacking normal thickening, featuring absence of stromal undulations and limbal crypts in cross-sections and sections parallel to the limbus, lack of visible limbal crypts in en face sections, loss of clear transition between the hyporeflective corneal epithelium and the hyperreflective conjunctival epithelium, and hyperreflective sub-epithelial fibrosis.

Due to difficulties to access primary bone marrow samples, human hematopoiesis has long remained far less characterized than in the mouse. Using an in vivo modeling approach of fetal hematopoiesis in humanized mice, we recently showed that human lymphoid cells stem from two functionally specialized populations of CD127- and CD127+ early lymphoid progenitors (ELP) that differentiate independently, respond differently to growth factors, undergo divergent modes of lineage restriction and generate distinct lymphoid populations. Our results demonstrate that, conversely to the mouse, human lymphopoiesis displays a bipartite developmental architecture.

There is a correlation between the success of the cord blood transplant and the numbers of HSC found in the unit of cord blood donation. The purpose of this analysis is to identify obstetric factors that may influence the quality of a cord blood unit taken during delivery.