Mesenchymal stromal cell therapy for systemic lupus erythematosus: mechanisms, clinical translation, and future directions

Systemic Lupus Erythematosus (SLE) is a complex autoimmune condition, fundamentally characterized by the loss of self-tolerance. This breakdown leads to the generation of autoantibodies and widespread inflammation that compromises multiple organs. A significant clinical challenge in SLE management is the lack of effective options for refractory disease, driving the pursuit of innovative treatments. Among these, mesenchymal stromal/stem cells (MSCs) have garnered significant attention due to their potent immunomodulatory and tissue-repair capabilities, highlighting their potential as a viable therapy. This review critically assesses the potential of MSCs in reconciling the unmet need for effective SLE therapies by examining their immunomodulatory mechanisms, clinical efficacy, and safety. MSCs reestablish immune tolerance through coordinated interactions with T and B cells, macrophages, and dendritic cells, predominantly facilitated by soluble factor secretion and extracellular vesicle release. In severe SLE, allogeneic MSC transplantation has demonstrated a capacity to induce durable remission, restore organ function, and improve survival rates, coupled with a reassuring safety profile. However, the field must still address issues of product standardization and long-term safety evaluation. Next-generation solutions-featuring engineered MSCs, iPSC-MSCs products, and vesicle-based therapies-hold the potential to usher in a new era of personalized SLE treatment. The conduct of large-scale randomized controlled trials is now imperative to definitively establish therapeutic efficacy and optimize clinical protocols.