Recent advances in stem cell biology and tissue engineering have profoundly renewed the field of liver organoids. More mature and complex, they now incorporate functional canalicular networks, metabolic gradients, and co-cultures including cholangiocytes, stellate cells, and macrophages. Advances in vascularization, bioprinting, and microfluidics are improving their stability and functionality, thereby enhancing their usefulness for disease modeling, pharmacology, personalized medicine, and future therapeutic applications.

Chemical burns are potentially blinding injuries and represent true ophthalmic emergencies that demand immediate evaluation and prompt initiation of treatment. Among these, alkali burns are more common than acid burns. Such injuries can cause widespread damage to the ocular surface epithelium, cornea, anterior segment structures, and limbal stem cells, often leading to permanent visual impairment in one or both eyes. We report a case of a 64-year-old female who developed diminution of vision following accidental chemical trauma with lime (calcium hydroxide). Clinical evaluation revealed deeply embedded corneal deposits without signs of acute infection or intraocular inflammation. She underwent surgical management involving superficial corneal scraping, thereby removing the necrotic tissue and suturing of a corneal patch graft. The surgery helped to restore ocular surface integrity, remove necrotic tissue, and promote healing, thereby reducing the risk of complications and preserving visual potential. Early surgical intervention and tailored postoperative care are essential for optimal outcomes in such cases.

Complete loss of both endocrine and exocrine functions of the pancreas results in the lifelong necessity for enzyme and insulin therapy, coupled with the possibility of immunosuppressant side effects following transplantation, representing the future for patients with hereditary pancreatitis (HP) after routine surgical intervention. One possible method for regenerating pancreatic cells and restoring their functioning is the application of stem cell therapy. The purpose of this narrative review is to compile the body of research on the application of stem cell therapy as a regenerative treatment for postpancreatectomy HP. Many pluripotent stem cells (PSCs), such as human embryonic stem cell-derived, and bone marrow (BM)-derived mesenchymal cells, are in different phases of study. These studies led to the creation of CRISPR VCTX210, VC-02 implants by ViaCyte. VX-880 by Vertex, in its phase 3 trial, used fully differentiated, allogenic pluripotent-stem-cell-derived islet therapy as a functional cure for type 1 diabetes. An allogeneic BM-derived mesenchymal stem cell (MSC), STEMCAP-1, developed by the Medical University of South Carolina (MUSC), is currently in its initial phase of trial. The terms "Hereditary Pancreatitis," "Pancreatectomy and insulin," and "Stem cell therapy" were used in a thorough search of PubMed, Google Scholar, and NIH. Thematic discussion and identification of pertinent material were conducted. Significant areas of divergence in the literature encompass the conventional management of HP, the justification for using Stem Cell Therapy, diverse clinical studies of beta-cell therapies, its burgeoning application in biotechnology and academic institutions, along with the implications for accessibility and economic factors. The enduring risk of insulin-dependent diabetes associated with HP can be mitigated through the regeneration of function with PSC-derived implants and MSC co-transplantation after pancreatectomy. Researchers may find this review useful in developing procedures for patient selection and monitoring, and clinicians may find it helpful in incorporating new treatments into patient care for HP.

Osteoarthritis, a degenerative disorder of the osteoarticular system, leads to progressive cartilage deterioration, resulting in pain and functional impairment. Its clinical presentation is heterogeneous, reflecting a diversity of phenotypes and molecular profiles. Risk factors include advanced age, female sex, obesity and joint trauma. Among emerging therapeutic strategies, mesenchymal stem cells (MSCs) offer promising prospects. These cells, derived from bone marrow, adipose tissue, and umbilical tissues, exhibit regenerative and immunomodulatory properties. In parallel, MSC-derived exosomes, which carry regenerative bioactive factors, represent another avenue of innovation, though their clinical application still requires further validation.

Exagamglogene autotemcel (Casgevy®) is an ex vivo gene therapy medicinal product (GTMP), derived from the patient's blood stem cells, intended for the treatment of beta-thalassemia. The complexity of this advanced therapy medicinal product (ATMP) required a specific pharmaceutical process at the university hospital of Lyon. This study aims to analyze potential failure modes throughout the Casgevy® process in order to prioritize interventions that need to be implemented.

Neural crest cells (NCCs) are a transient, multipotent cells that form at the border between the neural and non-neural ectoderm. Their formation is a finely choreographed process that can be compared to a developmental ballet. This process unfolds in four main stages: induction, specification, migration, and differentiation. Like versatile and talented performers, NCCs display a plasticity similar to that of stem cells, being capable of giving rise to multiple lineages. At the heart of NCC formation lies their gene regulatory network with signalling pathways and transcription factors kicking in at different stages of NCC development. Among these factors, transcription factor PAX3 plays a pivotal role in the establishment of NCCs, by intervening at various stages, from specification to differentiation.

Muscle regeneration in response to injury is a fine regulated process which relies on the ability of resident muscle stem cells (MuSCs) to activate, proliferate and differentiate to repair the injured myofibers. Muscle stem cells fate and correct skeletal muscle regeneration upon injury is guaranteed by a finely controlled crosstalk between transcriptional, epigenetic and metabolic regulation. Here, we explore the tight connection between cellular metabolism and epigenetic regulation during muscle stem cells fate focusing our attention on lysine demethylase enzymes.

Muscle stem cells are the gatekeepers of skeletal muscle integrity throughout life. They ensure muscle regeneration in case of a tissue injury. This process requires a precise reception of the environmental cues and an adequate cellular response from these specialized progenitor cells. They possess a primary cilium, a cellular antenna dedicated for reception and transduction of environmental signals. Several recent studies show that this organelle actively mediates signaling required for muscle stem cell quiescence maintenance, proliferation and fate. Here, we review the latest advances that revealed the role of the primary cilium in regulating the function of these muscle-resident stem cells.

Organoids have emerged as innovative three-dimensional (3D) in vitro models capable of reproducing the essential structural and functional characteristics of human organs. They offer an alternative between traditional two dimensions (2D) cell cultures and animal models. Derived from stem cells, organoids have an intrinsic capacity for self-organisation and morphogenesis, recapitulating the processes of embryonic development. Three elements are crucial for their generation: the origin of the stem cells, the extracellular matrix, and controlled exposure to morphogens. Among the most promising applications, neuromuscular organoids (NMOs) enable the co-differentiation of motor neurons, skeletal muscle cells, and Schwann cells from neuro-mesodermal progenitors. 3D NMO models and simplified 2D versions have been developed, complemented by assembloid-type approaches or microfluidic devices, facilitating the study of inter-cellular interactions and pharmacological testing. Produced from patients' iPS cells (induced pluripotent stem cells), NMOs offer a relevant platform for disease modelling, study of functional phenotypes and pharmacological screening in personalized medicine. Despite these advances, limitations remain, hindering the routine use of organoids. The standardization of protocols and the automation of analyses will enable the full translational potential of organoids to be exploited in the future.

Aplastic anaemia (AA) is a rare and life-threatening condition characterized by the failure of bone marrow to produce adequate blood cells. An autoimmune reaction of T lymphocytes against hematopoietic stem cells (HSCs) is the primary etiology. However, less commonly, a congenital deficiency or an acquired injury to these cells can also suppress their division and differentiation. Guidelines for practitioners to manage AA are frequently ambiguous. Close follow-up and monitoring are essential in managing patients with AA, necessitating physicians to comprehend the etiopathology of the disease. Clinical hematologists frequently provide specific treatments, but the physician must stay informed and cognisant of the latest management guidelines for the condition. In the management of AA, both specific and auxiliary modalities hold considerable significance. The databases that were used for the literature study were PubMed/Medline, Embase, Scopus, and Web of Science. Search terms included "Aplastic anaemia." Articles from after 2006 that were relevant to diagnosis and management instructions were the only ones that were used. The things that were not allowed were scholarly posters, abstracts, and studies with nonhuman subjects. In recent years, there has been a substantial evolution in the concepts related to treating AA. This is attributable to improved outcomes in both familial and nonfamilial donor HSC transplants, alongside current advancements in immunosuppressive and gene therapy. This review article presents the current scientific insights by emphasizing the diagnostic protocols and developments in therapies, including the impacts of gene therapy, immunosuppressive agents, and HSC transplantation.

Myelomeningocele (MMC), also known as Spina Bifida, is a congenital malformation of the spinal cord that results in a complex disability including motor deficits, sphincter disorders and cerebral anomalies. Benefit of fetal MMC surgery has been demonstrated since 2011, but remains partial, with persistent motor and sphincter disorders. We have developed an adjuvant treatment to improve spinal cord repair during fetal surgery: a patch composed of umbilical cord-derived mesenchymal stromal cells (UC-MSCs). Our in vitro and in vivo experiments in the ovine model of MMC demonstrated that the UC-MSC patch improves motor and urinary functions by promoting neuronal preservation in the spinal cord. We also confirmed the absence of maternal, fetal, and neonatal adverse effects. Our hypothesis is that this adjuvant therapy can similarly improve spinal cord repair in human fetuses, thereby improving clinical outcomes in affected children. The goal of the PRIUM-Cell clinical trial is to assess the use of UC-MSC patches as an adjuvant therapy during open fetal surgery for MMC in humans.

The Biomedicine Agency (ABM) is a public institution under the Ministry of Health, created by the Bioethics Law of July 29, 2004. The ABM specializes in three areas: organ and tissue donation, bone marrow donation, assisted reproduction, research on embryonic stem cells and human embryos, and medical genetics. Its main mission is to improve access to care and the quality of life of patients.

Acute graft-versus-host disease (GVHDa) is one of the leading causes of morbidity and mortality after allogeneic hematopoietic stem cell transplant (HSCT) patients. While the first-line consensus treatment has been based on systemic corticosteroid therapy for many years, ruxolitinib has recently been approved and has become the standard second-line treatment. Nevertheless, the effectiveness of ruxolitinib remains limited to 40 % of cortico-resistant patients, raising the crucial question of selecting a third-line treatment. Among the therapeutic modalities described, this workshop selected fecal microbiota transplantation (FMT), mesenchymal stromal cells (MSC) injection, and extracorporeal photopheresis (ECP) as the most promising or with a benefit/risk balance that favors their prescription at this stage. The workshop also highlighted the importance of research aimed at identifying markers or score calculations that guide toward a risk-adapted approach as early as possible. To date, aside from calprotectin, no marker or score is routinely used, but all are the subject of intense research. Finally, measures associated with specific treatment remain crucial, and new developments in dietary contributions, infection prophylaxis, and tissue regeneration are also addressed.

The aim of this article is to discuss alternatives to COBE2991® (Terumo BCT©) for the preparation of cell therapy products, in view of its planned cessation of commercialization in 2025. Cell therapy units need to find alternative methods in the face of regulatory restrictions and equipment obsolescence. Currently, COBE2991® (Terumo BCT©) is widely used in France, but its replacement will require multiple validations and adjustment of practices, as there is no single equivalent equipment. Recommendations for harmonizing these practices were discussed at a specific workshop in September 2024, following a survey of 25 French-speaking cell therapy centers.

RECENT ADVANCES IN THE TREATMENT OF PAROXYSTIC NOCTURNAL HEMOGLOBINURIA. Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder of hematopoietic stem cells, characterized by increased sensitivity to the lytic action of complement,corpuscular hemolytic anemia. Main complications are thrombotic events, aplastic anemia and clonal evolution. Development of terminal complement inhibitors (C5 inhibitors), improves prognosis of PNH patient through less thrombotic events, and improves quality of life by tapering transfusion requirement. However, 40% of patients have persisting punctual or regular transfusions needs under C5 inhibitors, due to extravascular hemolysis or insufficient complement blockade. In this context, proximal complement inhibitors (C3, B or D factors) have been developed and show resolution of extravascular hemolysis and maintenance of intravascular hemolysis control. Their place in the therapeutic strategy is still to be defined.

VEXAS SYNDROME. VEXAS (Vacuoles, E1 Enzyme, X-linked, Autoinflammatory, Somatic) syndrome is a recently described autoinflammatory syndrome, mostly affecting men above 50 years, caused by somatic mutation in the X-linked UBA1 gene. Patients present a broad spectrum of inflammatory manifestations (fever, neutrophilic dermatosis, chondritis, pulmonary infiltrates, ocular inflammation, venous thrombosis) with hematological involvement (macrocytic anemia, thrombocytopenia, vacuoles in myeloid and erythroid precursor cells, dysplastic bone marrow) which are responsible for significant morbidity and mortality. The therapeutic management is currently poorly codified, and based on two main approaches: controlling inflammatory symptoms by using corticosteroids, JAK inhibitors or tocilizumab, or targeting the UBA1-mutated hematopoietic population using azacitidine or allogeneic hematopoietic stem cell transplantation.

Intra-placental hepatic heterotopia is a rare lesion of embryonic development, poorly understood and often discovered incidentally during histopathological analyses. The morphological aspects of this lesion, as classically described, are relatively consistent in the literature, and several etiopathogenic hypotheses have been proposed, though none is entirely satisfactory. We report the case of a placenta presenting multiple foci of hepatic heterotopia identified within the fetal vascular network. The observation concerns a patient whose pregnancy was medically terminated at 20 weeks of amenorrhea due to a fetal polymalformative syndrome, for which a post-mortem diagnosis of Noonan syndrome was established. The pathological examination revealed three placental parenchymal lesions corresponding to heterotopic hepatic tissue. To date, no risk factors have been reported in the literature, nor have any known consequences on the child's development been identified. However, Noonan syndrome is recognized as a risk factor for the development of pediatric hepatic adenomatous lesions. The association of these two lesions may be coincidental or may support the etiopathogenic hypothesis of secondary migration of a hepatocellular adenoma within the fetal vascular network. The etiopathogenic mechanisms remain debated: an aberrant migration of hepatic tissue fragments through intra-vascular embolism, the entrapment of hepatocytes by the yolk sac, or even a co-evolution of the placenta and liver from stem cells. The absence of tumor characteristics and the histological similarity with embryonic hepatic tissue support the hypothesis of hepatic cell migration within the placenta.

Crohn's disease is a chronic inflammatory bowel disease that can lead to fibrostenotic complications. These strictures result from an imbalance between inflammation and excessive healing, leading to an abnormal accumulation of extracellular matrix and a progressive thickening of the intestinal wall. To date, no specific treatment is available to prevent or reverse intestinal fibrosis. The management of strictures primarily focuses on controlling inflammation and addressing obstructive complications through endoscopic balloon dilation, stricturoplasty, or intestinal resection. Current medical therapies, such as anti-TNF agents, can help reduce inflammation but have no direct impact on fibrosis. New therapeutic strategies are emerging, including TL1A inhibitors (duvakitug, tulisokibart), an ALK5 inhibitor (AGMB-129), and targeted AGR2 therapies (TH-009). Additionally, mesenchymal stem cells are being investigated in our hospital center in combination with endoscopic balloon dilation, aiming to assess their therapeutic potential. The development of effective anti-fibrotic therapies remains a critical medical need to improve the management of intestinal strictures and reduce the need for invasive procedures in Crohn's disease.

Highlighted by the COVID-19 pandemic, the study of respiratory infections is a global health priority. To this end, many preclinical in vitro study models have been developed to reproduce nasal, bronchial or alveolar respiratory epithelium. These models can be established from immortalised cell lines, primary culture or induced pluripotent stem cells (iPSC). They can also be constructed in various three-dimensional structures that are more or less physiological and easy to use. This synthetic review puts into perspective the advantages and limitations of these models, while highlighting their relevance for the study of the mechanisms of SARS-CoV-2 infection.

Beta-haemoglobinopathies are severe genetic anemias caused by mutations that affect adult haemoglobin production. Many therapeutic approaches aim to reactivate the expression of the fetal hemoglobin genes. To this end, the CRISPR/Cas9 system has recently been used to genetically modify patients' hematopoietic stem/progenitor cells ex vivo and reactivate fetal hemoglobin expression in their erythroid progeny. More than 70 patients with severe β-thalassemia and sickle cell disease have been treated with the Casgevy® therapy. Most have achieved a significant improvement of clinical phenotype, with high editing efficiency in hematopoietic cells associated with normal or near normal hemoglobin levels. While the long-term safety and efficacy of this powerful approach still need to be evaluated, new strategies are being developed to further improve therapeutic outcomes, reduce potential genotoxicity and lower the costs of therapy.