From donation to transplantation of hematopoietic stem cells, medullary origin, peripheral blood, placental or cord, legal provisions apply to the actors involved. Since 1994, the law on bioethics, its successive revisions and their implementing texts set the fundamental principles, rules and practical procedures to be followed.

The French unrelated stem cell donors registry is an operational entity developping bone marrow donation and transplantation. Its national role is linked to that of its international counterparts. Under public law in France, it is managed by the biomedicine agency.

The nurse coordinator of transplants is an essential function to organize and harmonize the care process for donors and recipients of haematopoietic stem cells. The missions assigned to this professional range from donor research to post-transplant follow-up of recipients.

Allogeneic stem cell transplant, used for the first time in 1950s, is the older immunotherapy which can be able to cure malignant hematologic diseases. Indications are becoming larger thanks to supportive care progress and larger donor availability, in particular with haplo-identical donors. Graft versus host disease and infections remain the main complications at the origin of high morbi-mortality (treatment-related mortality of 15 to 25%). Current major issue is to limit post-allogeneic relapse, especially thanks to targeted therapies and immunotherapy.

Graft-versus-host disease (GVHD) is a complication of hematopoietic stem cell transplantation. It frequently affects the digestive tract. Oesophageal damage is not part of its typical clinical picture. The objective of this study was to determine whether oesophageal lesions could be found in this condition.

In this article, we present the latest innovations to generate in vitro models of the glomerular filtration barrier. There is currently a growing interest for such model systems that allow to reduce the use of animal models. Methodologies to improve their physiological relevance have taken advantage of the development of induced pluripotent stem cells and of bioengineering, particularly tissue engineering. Here, we first introduce the methods to overcome the limitations of the currently used glomerular cells based on the use of stem cells. The different approaches to obtain podocytes, the most important cells in the glomerulus, are presented. Finally, we emphasize the importance of the glomerular microenvironment in maintaining the glomerular cell phenotype, which can be achieved by co-culturing different glomerular cells, integration of biomaterials mimicking the extracellular matrix and introduction of flows with microfluidics.

Bone is the most transplanted human tissue. Surgical interventions for bone repair are necessary for various pathologies such as nonunion, osteoporosis or osteonecrosis. Although autologous bone grafts remain the benchmark for bone regeneration, they unfortunately have a number of disadvantages: the need for a second intervention and the limited amount of tissue removed. Synthetic bone substitutes overcome some of these drawbacks, but their osteoinductive properties do not make it possible to treat significant bone losses. Cellular therapies based on mesenchymal stromal stem cells (MSC) in combination with bone substitutes may be alternatives to autologous bone grafting. It is in this context that we report the case of a patient with congenital dysplasia treated for non-union of the femur. The association of mesenchymal stem cells with bone substitute allowed us to obtain consolidation after 6 months.

Cultured Epithelial Autografts (CEAs), developed at the end of the 1970s from in vitro culture amplification of keratinocytes, have led to a therapeutic revolution in the treatment of major burns. The areas of improvement of the cultures initially involved the manufacturing processes (culture media, support matrices, etc.) and then clinical applications (use of a largely expanded allogeneic or autologous dermal bed). These advances have enabled burn centers (BC) using CEAs to obtain very satisfactory percentages of graft integration and survival of major burns patients. However, since CEAs are not without major drawbacks (fragility, high rate of infection, high cost, unstable scars), these pitfalls have restricted their use worldwide. As of 2014, CEAs produced by Genyzme Tissue Repair are no longer available in Europe, which has considerably reduced an indispensable therapeutic arsenal for severe and extensive burns. To overcome these therapeutic limitations, current research is focusing on techniques combining surgery, tissue engineering and cell therapy. The advent of regenerative medicine, based on the use of stem cells, in particular mesenchymal stem cells (MSC), can contribute to an improvement in the management of these massively burned patients (optimization of the environmental medium, attenuation of the systemic inflammatory response and the immunosuppressive effects of the burn, acceleration of tissue regeneration, etc.). Cell therapy, therefore, offers alternatives to CEAs, which must imperatively retain their place in the therapeutic arsenal, namely an effective emergency coverage technique that can be improved.

The use of dental stem cells has raised many hopes in the development of new treatments for neurodegenerative diseases. According to current statistics, about 1 in 6 people in the world would be affected by a neurological disease. This number continues to increase as the world's population ages, making neurodegenerative diseases probably the one of the major challenges of public health in the 21st century. Neurodegenerative diseases are characterized mainly by a progressive loss of cognitive abilities and patient autonomy related to loss and degeneration of neurons in brain structures. Unfortunately, today, the only treatments available for this type of disease do only relieve the symptoms, they do not treat them, and few clinical trials have been truly convincing to date. Hence, hope lies for these diseases in the development of other therapeutic approaches. As such, dental stem cells could be a promising area of research because of their rapid growth, their great capacity for differentiation into different types of cells (among neuronal ones for some of them) and how easy they can be obtained, without raising ethical issues as for example for embryonic stem cells.

Pelvic bone marrow is the site of nearly 50% of total hematopoiesis. Radiation therapy of pelvic lymph node areas, and cancers located near the bony structures of the pelvis, exposes to hematological toxicity in the range of 30 to 70%. This toxicity depends on many factors, including the presence or absence of concomitant chemotherapy and its type, the volume of irradiated bone, the received doses, or the initial hematopoietic reserve. Intensity modulated radiation therapy allows the optimisation of dose deposit on at risk organs while providing optimal coverage of target volumes. However, this suggests that dose constraints should be known precisely to limit the incidence of radiation side effects. This literature review focuses firstly on pelvic lymph node areas and bony volumes nearby, then on the effects of irradiation on bone marrow and the current dosimetric constraints resulting from it, and finally on hematological toxicities by carcinologic location and progress in reducing these toxicities.

Plants are fixed organisms with continuous development throughout their life and great sensitivity to environmental variations. They react in this way by exhibiting large developmental phenotypic plasticity. This plasticity is partly controlled by (phyto)hormones, but recent studies also suggest the involvement of epigenetic mechanisms. It seems that these two factors may interact in a complex way and especially in the stem cells grouped together in meristems. The objective of this review is to present the current arguments about this interaction which would promote developmental plasticity. Three major points are thus addressed to justify this interaction between hormonal control and epigenetics (control at the chromatin level) for the developmental plasticity of plants: the arguments in favor of an effect of hormones on chromatin and vice versa, the arguments in favor of their roles on developmental plasticity and finally the arguments in favor of the central place of these interactions, the meristems. Various perspectives and applications are discussed.

Infertility, early miscarriages and congenital malformations are major public health issues that are frequent and poorly understood. Until now, what is known about early human development originates from two main sources: studies of human embryos and studies of model animals. Although some molecular mechanisms are conserved, there are specific human features. Thus, it is necessary to study model animals that are close to humans in the phylogenetic classification, which led to the use of pre-established primate cell lineages. Currently, the only human embryos available come from In Vitro Fertilization, which leads to important limitations: these embryos are relatively few and must be destroyed after 14 days. This has led researchers to develop new strategies. Several teams used Embryonic Stem Cells or Induced Pluripotent Stem Cells and their in vitro auto-organization properties to recreate "embryos" and thereby study their development. These new strategies allow a reduced use of human embryos but new questions arise about the legal status of these new research "models". In the future, it would be important to update the different legislations and recommendations of the International Society for Stem Cell Research as science progresses to avoid any failing drift. The respect of recommendations as well as the maintenance of discussions between specialists and the general public will allow a better understanding of early human development and the establishment of innovative strategies to target health challenges.

markers in breast cancer stem cells, such as cluster of differentiation 10 (CD10), would be correlated with invasive and metastatic potential of several types of cancer, contributing to tumor growth and metastases. In patients with breast cancer, its prognostic value is still controversial, given the discrepancy of results. The purpose of the study was to study CD10 expression in stromal cells of patients with breast cancer as well as to evaluate the prognostic value of this expression.

Most prevalent cancers are of epithelial origin and their morbidity often results from secondary tumors. Cancer aggressiveness relates to intratumoral heterogeneity, including rare tumor initiating cells that share many features with adult stem cells. Both normal and cancer stem cells are characterized by their plasticity between epithelial and mesenchymal phenotypes, progressing through a series of reversible intermediates. While a core of regulators (Snail, Zeb1-2,...) is renowned to promote epithelial to mesenchyme transition (EMT), OvoL/Shavenbaby factors now emerge as a family of key epithelial stabilizers. Therefore, pro-EMT and OvoL/Shavenbaby transcription factors could provide a molecular rheostat to control stemness and epithelial-mesenchyme plasticity. We address this question in flies, in which the unique OvoL/Shavenbaby factor offers a powerful in vivo paradigm for functional analyses. Our results show that Shavenbaby is critical for adult stem cell homeostasis, and directly interacts with the Hippo pathway to protect stem cells from death.

CD34+ immunomagnetic positive selection allows for CD34+ hematopoietic progenitors separation from CD3+ lymphocytes subsets, usually from an apheresis product collected from a previously mobilized donor. This T-cell depleted stem cell graft is primarily intended for rare cases (around 2% of allotransplanted patients in France) of severe, persistent, symptomatic bi- or tri-cytopenia post-allotransplantation, in order to allow for hematologic reconstitution without increasing the risk of GvHD occurrence. Although semi-manual and complex, the process is of sufficient robustness to consistently generate a cellular product with distinctive features and specifications, based on iterative in-process quality controls, that are discussed within these guidelines.

Pathogenic variants of the gene NDE1 (Nuclear Distribution Element 1) in humans lead to microlissencephaly which associates a reduced head circumference and a simplified gyration. Microlissencephaly is the most severe deficit of neurogenesis described to date but its precise physiopathological mechanism is not yet well known. The NDE1 gene encodes a phosphoprotein that is essential to neurogenesis and that is expressed in various cell compartments of neuroblasts. More than 60 interaction partners with NDE1 have been reported, notably various proteins involved in formation of the mitotic spindle, in ciliation, in genome protection of dividing neuroblasts or even in apoptosis (like LIS1, dynein or cohesin), which are all avenues that we explore in this review.

Ex vivo production of human platelets have been pursued as an alternative measure to resolve limitations in the supply and safety of current platelet transfusion products. To this end, induced pluripotent stem cells (iPSCs) are considered an ideal global source, since they are not only pluripotent and self-renewing, but also are available from basically any person, have relatively few ethical issues, and are easy to manipulate. From human iPSCs, megakaryocyte (MK) lines with robust proliferation capacity have been established by the introduction of specified sets of genes. These expandable MKs are also cryopreservable and thus would be suitable as master cells for good manufacturing practice (GMP) grade production of platelets, assuring availability on demand and safety against blood-borne infections. Meanwhile, developments in bioreactors that physically mimic the in vivo environment and discovery of substances that promote thrombopoiesis have yielded competent platelets with improved efficiency. The derivation of platelets from iPSCs could further resolve transfusion-related alloimmune complications through the manufacturing of autologous products and human leukocyte antigen (HLA)-compatible platelets by manipulation of HLAs and human platelet antigens (HPAs). Considering these key advances in the field, HLA-deleted platelets could become a universal product that is manufactured at industrial level to safely fulfill almost all demands. In this review, we overview the ex vivo production of iPSC-derived platelets towards clinical applications, a production that would revolutionize the blood transfusion system.

For two decades, the prognostic of adult patients with ALL was improved based on pediatric-inspired protocols. These approaches based on less myelosuppressive drugs have led to improved response rates, decreased relapse rates, with a benefit in survival observed in patients aged up to 50-60-years-old. Therapeutic intensification came with a decrease in the use of allogeneic hematopoietic stem cell transplantation, with current indications mainly based on the level of measurable residual disease. Pediatric approaches are however limited in older patients or in patients with comorbidities, who are at greater risk to develop adverse effects especially to asparaginase. Future progresses will arise from personalized medicine including targeted therapy in some ALL oncogenic subgroups and immunotherapy. Monoclonal antibodies, bispecific antibodies, antibody drug conjugates and CAR-T cells have shown encouraging results in relapsed/refractory diseases. These strategies are now evaluated frontline in children and adults to further increase the quality of response, to limit the toxicity of treatments including allogeneic transplant. The objective of this review is to discuss the benefit and the limits of pediatric therapeutic strategies in adults and the perspectives offered by new approaches including immunotherapies.