Early morbimortality in autologous hematopoietic cell transplantation performed on outpatient basis in patients with autoimmune diseases: experience in 1700 patients
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The 2023 EBMT report on hematopoietic cell transplantation and cellular therapies. Increased use of allogeneic HCT for myeloid malignancies and of CAR-T at the expense of autologous HCT
In 2023, 47,731 HCT (20,485 (42.9%) allogeneic and 27,246 (57.1%) autologous) in 43,902 patients were reported by 696 European centers. 6042 patients received advanced cellular therapies, 4888 of which were CAR-T. Compared to the previous year there was an increase in CAR-T (+52.5%), in allogeneic HCT (+7.8%) but none in autologous HCT (+0.4%). Main indications for allogeneic HCT were myeloid (11,748; 60.7%), lymphoid malignancies (4,850; 25.0%), and non-malignant disorders (2558; 13.2%). Use of allogeneic HCT increased for AML (+12.1%) and for NHL (+11.0%), particularly in T-NHL (+25.6%). Main indications for autologous HCT were lymphomas (7890; 32.2%), PCD (14,271; 58.2%), and solid tumors (1608; 6.6%) with recovering numbers for autoimmune diseases. In patients with allogeneic HCT, the use of sibling donors increased by +1.0%, haploidentical donors by +11.7%, and unrelated donors by +11.1%. Cord blood HCT decreased again by −5.4%. Pediatric HCT activity increased slightly (5455; +0.1%) with differences between allogeneic (4111; −0.5%) and autologous HCT (1344: +1.7%). Use of CAR-T increased to a cumulative total of 13,927 patients including patients treated for autoimmune diseases. Overall, numbers show a complete recovery from the pandemic dip with increased cellular therapy at the expense of autologous HCT. Allogeneic HCT activity focuses on myeloid malignancies.
Energy metabolism in health and diseases
Energy metabolism is indispensable for sustaining physiological functions in living organisms and assumes a pivotal role across physiological and pathological conditions. This review provides an extensive overview of advancements in energy metabolism research, elucidating critical pathways such as glycolysis, oxidative phosphorylation, fatty acid metabolism, and amino acid metabolism, along with their intricate regulatory mechanisms. The homeostatic balance of these processes is crucial; however, in pathological states such as neurodegenerative diseases, autoimmune disorders, and cancer, extensive metabolic reprogramming occurs, resulting in impaired glucose metabolism and mitochondrial dysfunction, which accelerate disease progression. Recent investigations into key regulatory pathways, including mechanistic target of rapamycin, sirtuins, and adenosine monophosphate-activated protein kinase, have considerably deepened our understanding of metabolic dysregulation and opened new avenues for therapeutic innovation. Emerging technologies, such as fluorescent probes, nano-biomaterials, and metabolomic analyses, promise substantial improvements in diagnostic precision. This review critically examines recent advancements and ongoing challenges in metabolism research, emphasizing its potential for precision diagnostics and personalized therapeutic interventions. Future studies should prioritize unraveling the regulatory mechanisms of energy metabolism and the dynamics of intercellular energy interactions. Integrating cutting-edge gene-editing technologies and multi-omics approaches, the development of multi-target pharmaceuticals in synergy with existing therapies such as immunotherapy and dietary interventions could enhance therapeutic efficacy. Personalized metabolic analysis is indispensable for crafting tailored treatment protocols, ultimately providing more accurate medical solutions for patients. This review aims to deepen the understanding and improve the application of energy metabolism to drive innovative diagnostic and therapeutic strategies.
Conversion of placental hemogenic endothelial cells to hematopoietic stem and progenitor cells
Hematopoietic stem and progenitor cells (HSPCs) are critical for the treatment of blood diseases in clinic. However, the limited source of HSPCs severely hinders their clinical application. In the embryo, hematopoietic stem cells (HSCs) arise from hemogenic endothelial (HE) cells lining the major arteries in vivo. In this work, by engineering vascular niche endothelial cells (VN-ECs), we generated functional HSPCs in vitro from ECs at various sites, including the aorta-gonad-mesonephros (AGM) region and the placenta. Firstly, we converted mouse embryonic HE cells from the AGM region (aHE) into induced HSPCs (iHSPCs), which have the abilities for multilineage differentiation and self-renewal. Mechanistically, we found that VN-ECs can promote the generation of iHSPCs via secretion of CX3CL1 and IL1A. Next, through VN-EC co-culture, we showed that placental HE (pHE) cells, a type of extra-embryonic HE cells, were successfully converted into iHSPCs (pHE-iHSPCs), which have multilineage differentiation capacity, but exhibit limited self-renewal ability. Furthermore, comparative transcriptome analysis of aHE-iHSPCs and pHE-iHSPCs showed that aHE-iHSPCs highly expressed HSC-specific and self-renewal-related genes. Moreover, experimental validation showed that retinoic acid (RA) treatment promoted the transformation of pHE cells into iHSPCs that have self-renewal ability. Collectively, our results suggested that pHE cells possess the potential to transform into self-renewing iHSPCs through RA treatment, which will facilitate the clinical application of placental endothelial cells in hematopoietic cell generation.
Tissue macrophages: origin, heterogenity, biological functions, diseases and therapeutic targets
Macrophages are immune cells belonging to the mononuclear phagocyte system. They play crucial roles in immune defense, surveillance, and homeostasis. This review systematically discusses the types of hematopoietic progenitors that give rise to macrophages, including primitive hematopoietic progenitors, erythro-myeloid progenitors, and hematopoietic stem cells. These progenitors have distinct genetic backgrounds and developmental processes. Accordingly, macrophages exhibit complex and diverse functions in the body, including phagocytosis and clearance of cellular debris, antigen presentation, and immune response, regulation of inflammation and cytokine production, tissue remodeling and repair, and multi-level regulatory signaling pathways/crosstalk involved in homeostasis and physiology. Besides, tumor-associated macrophages are a key component of the TME, exhibiting both anti-tumor and pro-tumor properties. Furthermore, the functional status of macrophages is closely linked to the development of various diseases, including cancer, autoimmune disorders, cardiovascular disease, neurodegenerative diseases, metabolic conditions, and trauma. Targeting macrophages has emerged as a promising therapeutic strategy in these contexts. Clinical trials of macrophage-based targeted drugs, macrophage-based immunotherapies, and nanoparticle-based therapy were comprehensively summarized. Potential challenges and future directions in targeting macrophages have also been discussed. Overall, our review highlights the significance of this versatile immune cell in human health and disease, which is expected to inform future research and clinical practice.
Autologous haematopoietic stem cell transplantation for treatment of multiple sclerosis and neuromyelitis optica spectrum disorder — recommendations from ECTRIMS and the EBMT
Autologous haematopoietic stem cell transplantation (AHSCT) is a treatment option for relapsing forms of multiple sclerosis (MS) that are refractory to disease-modifying therapy (DMT). AHSCT after failure of high-efficacy DMT in aggressive forms of relapsing–remitting MS is a generally accepted indication, yet the optimal placement of this approach in the treatment sequence is not universally agreed upon. Uncertainties also remain with respect to other indications, such as in rapidly evolving, severe, treatment-naive MS, progressive MS, and neuromyelitis optica spectrum disorder (NMOSD). Furthermore, treatment and monitoring protocols, rehabilitation and other supportive care before and after AHSCT need to be optimized. To address these issues, we convened a European Committee for Treatment and Research in Multiple Sclerosis Focused Workshop in partnership with the European Society for Blood and Marrow Transplantation Autoimmune Diseases Working Party, in which evidence and key questions were presented and discussed by experts in these diseases and in AHSCT. Based on the workshop output and subsequent written interactions, this Consensus Statement provides practical guidance and recommendations on the use of AHSCT in MS and NMOSD. Recommendations are based on the available evidence, or on consensus when evidence was insufficient. We summarize the key evidence, report the final recommendations, and identify areas for further research.
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