An Overview of the Safety, Efficiency, and Signal Pathways of Stem Cell Therapy for Systemic Lupus Erythematosus

Abstract

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organs and tissues. Mesenchymal stem cells (MSCs) are considered a good source for autoimmune disease and hematological disease therapy. This review will summarize the efficacy, safety, and mechanisms of MSC therapy for SLE. MSC therapy can reduce anti-dsDNA, antinuclear antigen (ANA), proteinuria, and serum creatinine in SLE patients. In animal models of SLE, MSC therapy also indicates that it could reduce anti-dsDNA, ANA, proteinuria, and serum creatinine and ameliorate renal pathology. There are no serious adverse events, treatment-related mortality, or tumor-related events in SLE patients after stem cell treatment. MSCs can inhibit inflammatory factors, such as MCP-1 and HMGB-1, and inhibit inflammation-related signaling pathways, such as the NF-κB, JAK/STAT, and Akt/GSK3β signaling pathways, to alleviate the lesions in SLE.

Mesenchymal stem cell transplantation as a potential therapy for refractory lupus nephritis: A systematic review

“…All studies appraised in this systematic review successfully demonstrated significant improvement in SLEDAI scores. Besides reducing proinflammatory cytokines, such as IL‐23, IL‐17, monocyte chemoattractant protein‐1, and high‐mobility group box chromosomal protein 1, MSCs can also promote upregulation of anti‐inflammatory cytokines, including IL‐4, prostaglandin E2, transforming growth factor beta, and IL‐10 23 . The resulting anti‐inflammatory effect leads to delayed organ damage and reduced disease activity.…”

Immunogenicity of mesenchymal stromal/stem cells

“…In a clinical trial‐based study, transplantation of allogeneic UC‐MSCs in patients with type 2 diabetes resulted in significant improvements in diabetes status, reductions in insulin requirements and insulin independence during follow‐up, and no immediate or long‐term side effects associated with cell infusion during treatment 106 . MSCs treatment also reduced anti‐dsDNA, antinuclear antigens, proteinuria, and serum creatinine in systemic lupus erythematosus (SLE) patients without serious adverse events, treatment‐related mortality, or tumour‐related events 107,108 . There are also many reports of successful application in other system intractable diseases 109–111 …”

“…106 MSCs treatment also reduced anti-dsDNA, antinuclear antigens, proteinuria, and serum creatinine in systemic lupus erythematosus (SLE) patients without serious adverse events, treatment-related mortality, or tumour-related events. 107,108 There are also many reports of successful application in other system intractable diseases. [109][110][111] In conclusion, allogeneic MSCs therapy has a good prospect for the treatment of a variety of difficult clinical diseases.…”

Evaluation of the Therapeutic Potential of Mesenchymal Stem Cells (MSCs) in Preclinical Models of Autoimmune Diseases

“…However, heterogeneous presentation of lupus in humans presents a challenge, and mouse models may not represent a complete spectrum of pathogenesis but only a subset of changes observed in the human population [ 84 ]. A comprehensive review of the safety, efficacy, and signal pathways of stem cell therapy of SLE [ 68 ] suggested an immense potential for clinical applications. Allogenic MSC transplantation with peripheral blood MSCs in three lupus nephritis patients resulted in decreased serum creatinine levels.…”

“…MSCs have the potential to regulate the immune system and control inflammation by inhibiting the activation of NF-κB and JACK/STAT and Akt/GSK3β signalling pathways to ameliorate SLE lesions [67]. Hence, MSCs have been extensively explored for the treatment of SLE in experimental animals [29,68] and human patients [2,8]. MSCs exert immunosuppressive effects through proinflammatory cytokine secretion and inhibiting lymphocyte activation and 3 Stem Cells International proliferation.…”