**Abstract**

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune inflammatory disorder with considerable clinical heterogeneity and a prevalence of 26 to 52 out of 100,000. In autoimmune diseases, such as SLE, the immune system loses its ability to distinguish between self and other. Treatment of SLE is challenging because of clinical heterogeneity and unpredictable disease flares. Currently available treatments, such as corticosteroids, cyclophosphamide (CYC), and other immunosuppressive or immunomodulating agents, can control most lupus flares but a definitive cure is rarely achieved. Moreover, standard therapies are associated with severe side effects, including susceptibility to infections, ovarian failure, and secondary malignancy. Alternative therapeutic options that are more efficacious with fewer side effects are needed to improve long-term outcome. Mesenchymal stem cells/multipotent stromal cells (MSCs), which secrete immunomodulatory factors that help restore immune balance, could hold promise for treating these diseases. Because MSCs do not express major histocompatibility complex II (MHC-II) or costimulatory molecules, they are also "immunologically privileged" and less likely to be rejected after transplant. Stem cells are defined as a class of undifferentiated cells in multicellular organisms that are pluripotent and self-replicating. MSCs are promising in regenerative medicine and cell-based therapies due to their abilities of their self-renewal and multilineage differentiation potential. Most importantly, MSCs have immunoregulatory effects on multiple immune system cells. While some studies report safety and efficacy of allogeneic bone marrow and/or umbilical cord MSC transplantation (MSCT) in patients with severe and drug-refractory systemic lupus erythematosus (SLE), others found no apparent additional effect over and above standard immunosuppression. The purpose of this chapter is to discuss immune modulation effects of MSCs and the efficacy of MSCs treatments in SLE.

**Keywords:** Mesenchymal stem cell, Cell therapy, Systemic Lupus Erythematosus, Clinical trials, Lupus nephritis
