An Update for Mesenchymal Stem Cell Therapy in Lupus Nephritis

Background: Lupus nephritis (LN) is the most severe organ manifestations of systemic lupus erythematosus (SLE). Although increased knowledge of the disease pathogenesis has improved treatment options, outcomes have plateaued as current immunosuppressive therapies have failed to prevent disease relapse in more than half of treated patients. Thus, there is still an urgent need for novel therapy. Mesenchymal stem cells (MSCs) possess a potently immunosuppressive regulation on immune responses, and intravenous transplantation of MSCs ameliorates disease symptoms and has emerged as a potential beneficial therapy for LN. The objective of this review is to discuss the defective functions of MSCs in LN patients and the application of MSCs in the treatment of both LN animal models and patients. Summary: Bone marrow MSCs from SLE patients exhibit impaired capabilities of migration, differentiation, and immune regulation and display senescent phenotype. Allogeneic MSCs suppress autoimmunity and restore renal function in mouse models and patients with LN by inducing regulatory immune cells and suppressing Th1, Th17, T follicular helper cell, and B-cell responses. In addition, MSCs can home to the kidney and integrate into tubular cells and differentiate into mesangial cells. Key Messages: The efficacy of MSCs in the LN treatment remains to be confirmed, and future advances from stem cell science can be expected to pinpoint significant MSC subpopulations, as well as specific mechanisms of action, leading the way to the use of more potent stimulated or primed pretreated MSCs to treat LN.

Automated summary

Bone marrow MSCs from SLE patients show impaired capabilities of migration, differentiation, and immune regulation, as well as a senescent phenotype. Allogeneic MSCs suppress autoimmunity and restore renal function in mouse models and LN patients by inducing regulatory immune cells and suppressing certain immune cell responses. Moreover, MSCs can migrate to the kidney, integrate into tubular cells, and differentiate into mesangial cells. There is still a need for further confirmation of the efficacy of MSCs in LN treatment, and advancements in stem cell science may lead to the use of more potent stimulated or primed pretreated MSCs for LN therapy.