Comparative efficacy of mesenchymal stromal cells versus multi-target therapy in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) treatment requires balancing rapid autoimmunity control with long-term organ repair. Mesenchymal stromal cells (MSCs) and multi-target pharmacotherapy represent fundamentally different therapeutic strategies. MSCs exert context-dependent immunomodulation, whereas the latter relies on broad immunosuppression. This contrast makes direct comparison essential to guide therapy decisions. Here, we conducted a head-to-head evaluation of these two strategies in a lupus murine model. Lupus mice received either umbilical cord-derived MSCs or TMP (tacrolimus, mycophenolate mofetil and prednisone) over an 8-week period. Both treatments significantly alleviated core lupus symptoms, including enlarged spleen/lymph nodes and excessive antibody production. However, MSCs showed greater efficacy in suppressing pathogenic autoantibodies, repairing podocyte damage, and increasing protective regulatory T cells in the kidney and peripheral tissues. TMP more effectively reduced peripheral circulating immune cells. These findings highlight the complementary therapeutic profiles of MSCs and multi-target pharmacotherapy in SLE, providing a critical rationale for personalized treatment stratification.