Exosomes are small extracellular vesicles (EVs) generated through the endosomal pathway that mediate intercellular communication by transferring proteins, lipids, and regulatory RNAs. In parallel, the NLRP3 inflammasome is a key signaling platform of the innate immune system that integrates cellular stress signals to drive inflammatory responses. Recent studies suggest that exosome biology and NLRP3 signaling intersect at fundamental levels of cell organization. On one hand, inflammasome activation can promote exosome biogenesis and secretion through caspase-1-dependent remodeling of intracellular trafficking, including cleavage of Rab-interacting lysosomal protein (RILP) and redistribution of multivesicular bodies (MVBs). These processes influence the selective loading of exosomal cargo, notably miRNAs, through sequence-dependent mechanisms involving RNA-binding proteins and the endosomal sorting machinery. Conversely, exosomes can modulate inflammasome activity in recipient cells by delivering regulatory molecules that affect NLRP3 priming and signaling. Although exosome release is increased in several inflammatory disorders, including ischemia/reperfusion injury, diabetes and neurodegenerative disease, the mechanistic relationship between exosome pathways and NLRP3 remains incompletely understood. In addition to their pathogenic and diagnostic relevance, exosomes are increasingly being explored as innovative acellular biologics and therapeutic delivery platforms due to their immunomodulatory and regenerative properties. In particular, mesenchymal stem cell (MSC)-derived exosomes have shown promising anti-inflammatory effects through modulation of NLRP3 pathways in preclinical models of kidney, cardiovascular, neurological and inflammatory diseases. Here, we review current evidence connecting NLRP3 inflammasome activation to EV trafficking, exosome formation, and cargo selection, and discuss how exosome-mediated communication shapes inflammasome signaling across cells and tissues in health and disease.
Genitourinary syndrome of menopause (GSM) is a common hypoestrogenic condition marked by vulvovaginal atrophy and lower urinary tract symptoms that significantly impair quality of life in peri- and postmenopausal women. Although local estrogen therapy remains the standard of care, its use is constrained by contraindications, adherence challenges, and concerns regarding long-term safety, particularly in women with estrogen-sensitive conditions. As a result, interest has grown in regenerative, non-hormonal alternatives. Stem cell-based therapy, particularly using mesenchymal stem cells (MSCs), has emerged as a potential therapeutic strategy for restoring urogenital tissue structure and function. The current body of evidence largely consists of preclinical studies, small clinical case series, and investigations in related but distinct conditions, which provide potential mechanistic insights. Preclinical studies suggest that MSCs from adipose tissue, bone marrow, and umbilical cord promote vaginal epithelial regeneration through paracrine mechanisms, including angiogenesis, immunomodulation, extracellular matrix remodeling, and restoration of local estrogen signaling and vaginal microbiota. To date, current clinical studies have not provided direct evidence on the efficacy of characterized MSC-based therapies specifically in GSM populations. Early clinical evidence, primarily involving adipose-derived tissue products such as micro-fragmented adipose tissue, reports improvements in symptoms overlapping with GSM, including vaginal dryness, dyspareunia, urinary symptoms, and sexual function, with benefits lasting up to two to three years after a single treatment and no serious adverse events reported. However, available data are limited by small cohorts, the absence of randomized trials, and regulatory variability. This review summarizes current evidence and outlines key scientific, ethical, and regulatory challenges that must be addressed to guide future research and clarify the therapeutic potential of MSC-based approaches in GSM, ultimately enabling translation.
Atopic dermatitis (AD) is a common inflammatory skin disorder which presents with recurrent eczematous lesions and itching. Its pathophysiology is complex and multifactorial. Alterations in cell-mediated immune responses, barrier dysfunction, environmental aspects and IgE-mediated hypersensitivity are all involved. This review aims to provide the clinician with an update on the impact that Th2 inflammation can have on growth and osteoimmunology. The potential adverse or protective effects brought on by the many therapies administered in this condition are also considered. Moreover, through this analysis, we aim to show how, by inhibiting the IL-4 and IL-13 signaling pathways—fundamental in the T helper 2 (Th2) immune axis and in AD pathogenesis—dupilumab may exert a protective role on growth and osteoimmunology in moderate-to-severe AD, particularly in young patients. This focus is essential for the correct, safe management of patients with Th2 inflammation.
Temporomandibular joint osteoarthritis (TMJ-OA) is a multifactorial degenerative disorder characterized by progressive cartilage degradation, subchondral bone remodeling, and chronic inflammation, leading to pain and functional impairment in affected individuals. Despite its clinical impact, effective disease-modifying treatments remain limited, highlighting the need for innovative therapeutic approaches for treating this condition in the future. This manuscript examines the biological rationale, clinical applications, and therapeutic potential of platelet-rich plasma (PRP) and injectable platelet-rich fibrin (i-PRF) in the management of TMJ-OA. As autologous platelet-derived biomaterials, PRP and i-PRF contain high concentrations of growth factors and bioactive molecules that can modulate inflammatory responses and support tissue repair. PRP is associated with a relatively rapid release of these mediators, whereas i-PRF forms a fibrin matrix that may enable a more sustained release profile. Current clinical evidence suggests that both therapies show potential to contribute to pain reduction and may facilitate improvements in mandibular function. However, substantial heterogeneity in preparation protocols, study designs, and outcome measures limits the comparability and generalizability of these findings to the general population. Overall, PRP and i-PRF represent promising, minimally invasive regenerative strategies for managing TMJ-OA.
Fetal therapy has evolved into a rapidly advancing field with the potential to alter the natural history of many severe congenital and genetic disorders before irreversible injury occurs. Progress in prenatal imaging, molecular diagnostics, and fetal intervention techniques now enables the earlier identification of disease and, in select settings, targeted prenatal treatment. This review synthesizes the current landscape of fetal therapies, spanning established surgical interventions for structural anomalies and emerging biologic and molecular approaches, including enzyme replacement therapy, stem cell-based strategies, gene therapy, and gene editing. The intrauterine environment provides a distinct therapeutic context, with developmental plasticity, immune immaturity, enhanced tissue accessibility, and relatively permissive central nervous system exposure that together define a time-sensitive window for intervention. Preclinical studies and early clinical experience across both structural anomalies and genetic disorders, including lysosomal storage disorders, osteogenesis imperfecta, and spinal muscular atrophy, support the premise that prenatal treatment can preserve organ development and improve pediatric outcomes. However, translation remains constrained by procedural risks, uncertainty regarding long-term safety and durability, ethical and regulatory complexities, and challenges with equitable access, alongside the need for robust comparative evidence versus early postnatal therapy. As the field advances, multidisciplinary collaboration, rigorous trial design with meaningful developmental endpoints, and ethically grounded implementation frameworks will be essential to guide responsible clinical adoption and maximize benefit for children and families.
