Changing practices and the limited use of cord blood units as a source of cells for allogeneic hematopoietic stem cell transplants (HSC) led us to reconsider the recommendations established in 2011 and 2012, and to propose an update incorporating recent bibliographic data. If HLA compatibility was until now established at low resolution for HLA-A and B loci, and at high resolution for HLA-DRB1, the recent papers are converging towards an increase in the level of resolution, making way for a compatibility now defined in high resolution for all the considered loci, and the inclusion of the HLA-C locus, in order to establish a level of HLA compatibility on 8 alleles (HLA-A, B, C and DRB1). The CD34+ dose is a determining factor in hematopoietic reconstitution but it is not correlated with the total nucleated cells content. This is why we recommend taking these two data into account when choosing a cord blood unit. The recommendations established by our group are presented as a flow chart taking into account the characteristics of the underlying pathology (malignant or non-malignant), the cell dose and the HLA compatibility criteria, as well as criteria linked to the banks in which units are stored.

Lipofibroblasts form a sub-population of fibroblasts located in the mesenchymal alveolar stem cell niche. They show close proximity with alveolar epithelial type 2 cells and play a key role in alveolar development and lung homeostasis. Their role in various diseases such as acute respiratory distress syndrome, pulmonary fibrosis and emphysema is progressively better understood. Through the activation of signaling pathways such as PPARg lipofibroblasts may help to induce endogenous alveolar regeneration.

Severe asthma patients with persistent airflow obstruction are characterized by functional obstruction due to mucus plugs containing mucins, fibrin, and eosinophil derived Charcot- Leyden crystals. The molecular mechanisms underlying this endotype are not clearly understood. Developing new models is crucial to respiratory research insofar as critical differences exist between human and rodent airway epithelium. We (and other teams) have shown that it is possible to reconstitute in vitro a complex and functional airway epithelium displaying all the features described in vivo from human-induced pluripotent stem cells (hiPSC). Our aim is to establish a human in vitro model of severe asthma that will recapitulate airway epithelium remodeling and mucus plugs.

Totipotency is the ability of a cell to generate a whole organism, a property that characterizes the first embryonic cells, such as the zygote and the blastomeres. This review provides a retrospective on the progress made in the last decade in the study of totipotency, especially with the discovery of mouse ES cells expressing markers of the 2-cell stage (2C-like cells). This model has greatly contributed to a better understanding of the molecular mechanisms involved in totipotency (pioneer factors, epigenetic regulation, splicing, nuclear maturation). 2C-like cells have also paved the way for the development of new cellular models of human totipotency.

Oral buccal tissues, including bone and mucosa, have unique properties. Oral mucosal fibroblasts and jaw osteoblasts, both derived from Cranial Neural Crest cells, play a key role in healing and repair. These cells express a specific repertoire of genes with their regenerative properties, but also craniofacial diseases. Understanding these tissues holds clinical promise for tissue regeneration and repair of bone and mucosal defects. These multidisciplinary advances also offer potential for better management of periodontal-related conditions and improved oral health.

Chronic Granulomatosis Disease (CGD) is an inherited immune deficiency due to a mutation in the genes coding for the subunits of the NADPH oxidase enzyme that affects the oxidative capacity of phagocytic cells. It is characterized by increased susceptibility to bacterial and fungal infections, particularly Aspergillus, as well as complications associated with hyperinflammation and granulomatous tissue infiltration. There exist two types of frequently encountered pulmonary manifestations: (1) due to their being initially pauci-symptomatic, possibly life-threatening infectious complications are often discovered at a late stage. Though their incidence has decreased through systematic anti-bacterial and anti-fungal prophylaxis, they remain a major cause of morbidity and mortality; (2) inflammatory complications consist in persistent granulomatous mass or interstitial pneumoniae, eventually requiring immunosuppressive treatment. Pulmonary complications recurring since infancy generate parenchymal and bronchial sequelae that impact functional prognosis. Hematopoietic stem cell allograft is a curative treatment; it is arguably life-sustaining and may limit the morbidity of the disease. As a result of improved pediatric management, life expectancy has increased dramatically. That said, new challenges have appeared with regard to adults: difficulties of compliance, increased inflammatory manifestations, acquired resistance to anti-infectious therapies. These different developments underscore the importance of the transition period and the need for multidisciplinary management.

Immunotherapy strategies have revolutionized the management of a significant number of patients in recent years, whether they are undergoing treatment for hematologic malignancies or solid tumors. This therapeutic class is extensive, ranging from antibodies targeting immune checkpoint molecules to adoptive cell therapy strategies, including bispecific antibodies and anticancer vaccines. All these strategies are currently in active development. Adoptive cell therapy involves the infusion of normal or genetically modified immune cells into a patient with the aim of restoring strong antitumor immunity, primarily associated with the cytotoxicity of T lymphocytes. Currently, there are three major adoptive cell therapy strategies: allogeneic hematopoietic stem cell transplantation, CAR-T cell therapy, and TCR-T cell therapy. The objective of this article is to describe the mechanisms of action of these three strategies as well as their current advantages, limitations and constraints.

Muscle stem cells (MuSCs) are skeletal muscle resident stem cells responsible of skeletal muscle regeneration and tissue integrity maintenance. It is now becoming prominent that the ability of MuSCs either to self-renew or differentiate is affected by cellular metabolism. Recently, a study elucidated that lipid droplets (LDs) are novel key regulators of MuSC fate. Indeed, LDs distribute differently depending on MuSC state during the regeneration process, as LDLow MuSCs are more proned to self-renew while LDHigh MuSCs commit to differentiation. Therefore, these findings highlight that the LD turnover is necessary for MuSC fate decision, opening the question of the molecular mechanism underlying lipid metabolism regulation of MuSC fate determination.

Fibro-adipogenic progenitors (FAPs) are resident mesenchymal stromal cells (MSCs) of skeletal muscle. They play a crucial role in muscle homeostasis and regeneration through their paracrine activity. Recent technological advances in single-cell RNA sequencing have allowed the characterization of the heterogeneity within this cell population. In this article, we will present the different subpopulations of FAPs under basal, injury, or degenerative conditions, as well as their associated functions in mice and humans. We will then discuss the potential extramuscular origin of a post-injury FAP population. Indeed, our recent work demonstrates that MSCs from adipose tissue, infiltrating the muscle, could contribute to FAP heterogeneity.

Adult skeletal muscle is composed of thousands of fibers (also called myofibers) that contract thus allowing voluntary movements. Following an injury, muscle stem cells, surrounding the myofibers, activate, proliferate, and differentiate to form de novo myofibers. These steps constitute a process called adult (or regenerative) myogenesis. This process is possible thanks to various transcription factors sequentially expressed and regulated by epigenetic factors that modulate the chromatin and therefore lead to the regulation of gene expression. Gene expression changes consequently affect the fate of muscle stem cells. Histone Lysine Methyltransferases methylate some histones involved in the repression of gene expression. We describe here the role of SETDB1 during adult myogenesis, notably its role during muscle stem cell differentiation.

Links between aging and epigenetics have been revealed by bio-mathematicians. Methylation of cytosine, which is a characteristic of the epigenome, varies with age on some ADN loci, increasing or decreasing. From an analysis of the methylome, algorithms giving an "epigenetic age" were obtained, strongly correlated with the age. Surprisingly, this approach could be applied consistently to different tissues or unpurified cells. It was successfully applied to tissues of 185 mammalian species. The epigenetic age of embryonic pluripotent stem cells is nearly zero and it decreases to "ground zero" during gastrulation. The average methylation curve as a function of age allows discrimination between slowly or rapidly aging individuals. At the present time, more than 10 different epigenetic clocks have been proposed for medical applications. The localization of aging-sensitive CpG pairs on the genome revealed networks of "co-methylation", involved in different functions such as regulation of morphogenesis or cell differentiation. From these studies, aging appears as a continuous process, with the epigenetic clock starting to "tick" in the embryo.

What if we changed our point of view? What if we approached endodontics from a biological perspective rather than a mechanistic one? What if, in the case of pulpal tissue necrosis, we were to consider an alternative to apexification therapies? Is pulp tissue regeneration now possible?

This article summarizes Françoise Dieterlen's major scientific discoveries about the hematopoietic and endothelial systems during her 40 years' career. Her most remarkable achievements include notably the demonstration of an intraembryonic source of hematopoietic stem cells, the characterization of the polarization of the aorta, the identification of a hemogenic endothelium as well as that of the allantois as an organ of hematopoietic amplification in the mouse embryo, and the demonstration of the existence of a hemogenic endothelium capable of generating hematopoietic stem cells in the bone marrow of the chicken and mouse embryo. While this last discovery was not made directly by Françoise Dieterlen, it was inspired by the many conversations I have had with her and the lessons she has taught me throughout my career. Her rich career will forever shape the field of hematopoietic development, in which she will remain a guiding figure.

Muscle regeneration in response to injury or exercise relies on the ability of muscle stem cells to proliferate and differentiate to repair the damage. In the absence of damage, muscle stem cells are quiescent: they do not proliferate and have a very low metabolism. Recent studies have linked the metabolic state of the adult muscle stem cell to its epigenetic regulation. This article synthesizes the known concepts about histone modifications and metabolic pathways found in quiescent muscle stem cells, as well as the metabolic and epigenetic changes leading to muscle stem cell activation in response to injury. Here, we discuss the heterogeneity in quiescent stem cell metabolism and compare the metabolism of quiescent and activated muscle stem cells, and describe the epigenetic changes related to their activation. We also discuss the involvement of SIRT1, an important effector of muscle stem cells metabolism, together with the effects of aging and caloric restriction.

MANAGEMENT OF SECONDARY LESIONS IN ANO-PERINEAL CROHN'S DISEASE. Anoperineal involvement in Crohn's disease is common and affects around 1/3 of patients during their disease. It constitutes a pejorative factor with an increased risk of permanent colostomy and proctectomy and is associated with a major deterioration in quality of life. Secondary anal lesions in Crohn's disease are fistulas and abscesses. They are difficult to treat and often recurrent. A multidisciplinary medico-surgical management in several stages is essential. The classic sequence is based on a first phase of drainage of fistulas and abscesses, a second phase of medical treatment based primarily on anti-TNF alpha and finally a third phase of surgical closure of the fistula tract(s). Conventional closure techniques such as biologic glue, plug, advancement flap and intersphincteric ligation of the fistula tract have limited effectiveness, are not always feasible, require technical skills and some have an impact on anal continence. In recent years, we have witnessed a real enthusiasm generated by the arrival of cell therapy. This has not spared proctology since adipose-derived allogeneic mesenchymal stem cells have had Marketing Authorisation and have been reimbursed in France since 2020 in the treatment of complex anal fistulas in Crohn's disease after failure of at least one biologic therapy. This new treatment offers an additional alternative in patients often in a situation of therapeutic impasse. Preliminary results in real life are satisfactory with a good safety profile. However, it will be necessary to confirm these results in the longer term and to work to determine the profile of the patients who could benefit the most from this expensive therapy.

SPARING THE SPHINCTER. Fistulotomy is the most used treatment for anal fistula. It is very effective with a cure rate of over 95% but carries a risk of incontinence. This has led to the development of various sphincter sparing techniques. The injection of biological glue or paste and the insertion of a plug have disappointing results and are expensive. The rectal advancement flap is still practised because of its cure rate of around 75% but it may result in some incontinence. Intersphincteric ligation of the fistula track and laser treatment are widely practised in France with cure rates between 60 and 70%. Video-assisted anal fistula treatment as well as injections of adipose tissue, stromal vascular fraction, platelet-enriched plasma and/or mesenchymal stem cells are emerging techniques for which even better results are expected.

Inhibition of androgen signaling is the gold standard treatment of benign prostate hyperplasia and prostate cancer. Despite the initial response to these treatments, therapeutic resistance is ultimately observed in most patients. Single cell RNAseq studies have shown that castration-tolerant luminal cells share several molecular and functional features with cells identified as luminal progenitor in physiological conditions. The increased prevalence of luminal progenitor-like cells in tumor contexts might result from their intrinsic androgen-independence and from the reprogramming of differentiated luminal cells into a castration-tolerant state. Thus, it is currently hypothesized that the luminal progenitor molecular profile might constitute a functional hub for cell survival in androgen deprivation context, a prerequisite for tumor regrowth. Therapeutic intervention interfering with luminal lineage plasticity is a promising approach to prevent prostate cancer progression.

Allogeneic hematopoietic stem cell transplantation (HCT) and CAR-T cells therapy are treatments with curative aim for certain hematological malignancies, refractory or relapse. Nevertheless, they carry the risk of morbidity and mortality and may have a significant psychosocial impact, particularly for HCT. It is therefore necessary to identify psychological difficulties and social problems, as well as the patient's resources, and those of his entourage, in order to improve his overall management. The objective of this evaluation is not to pose contraindications to treatments, but to adapt the personalized care project. This identification must be carried out early on in the pre-HCT assessment journey to enable the implementation of appropriate actions by the various care providers. Based on a review of the literature, we designed a psychosocial data collection grid that can be initiated in pre-transplant and updated by accompanying the patient at each stage of follow-up (discharge from hospital, day-hospital follow-up, D100 evaluation). This grid is divided into 3 axes: socio-family context, psychological and somatic aspects. This tool allows the traceability of the interventions of different professionals and is a support for multidisciplinary exchanges.