Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder in which an overactive immune system attacks multiple organs, including the kidneys, skin, and nervous system. Conventional medications such as corticosteroids, hydroxychloroquine, and immunosuppressants can control inflammation but do not cure the disease or prevent long-term damage. For many patients with severe or treatment-resistant SLE, cell-based regenerative therapy offers a new therapeutic pathway aimed at immune restoration rather than suppression.
The review by Dao et al. (2024) highlights several forms of cell therapy for lupus, including hematopoietic stem cell transplantation (HSCT), mesenchymal stem cell (MSC) therapy, and chimeric antigen receptor (CAR) T-cell therapy, along with experimental approaches such as regulatory T-cell (Treg) and natural killer (NK) cell theray.
Hematopoietic Stem Cell Transplantation (HSCT)
HSCT aims to reset the immune system by eradicating autoreactive cells and reconstituting immune balance. It has produced long-term drug-free remissions in severe SLE cases, with 50–66% of patients remaining relapse-free after 5 years. However, the high risks of infection, relapse, and transplant-related mortality limit its widespread use. Experts recommend HSCT primarily for severe refractory lupus under strict medical supervision.
Mesenchymal Stem Cell (MSC) Therapy
Among all cell therapies, MSC stem cell therapy is the most extensively studied and clinically applicable for SLE. MSC stem cell therapy can self-renew, differentiate into various cell types, and modulate both innate and adaptive immune responses. They suppress overactive T and B cells, promote regulatory T-cell populations, and release anti-inflammatory cytokines and growth factors such as IL-10 and TGF-β.
Clinical studies show that MSC therapy for lupus can significantly reduce SLEDAI and BILAG scores while improving renal function, especially in patients with lupus nephritis. A meta-analysis of 12 clinical studies involving 586 patients reported clear reductions in disease activity within 12 months of MSC infusion, with excellent safety and tolerability.
Umbilical cord–derived MSCs (UC-MSCs) have emerged as a preferred source due to their strong immunomodulatory effects, accessibility, and lack of ethical concerns. In contrast, autologous MSC stem cell therapy from SLE patients often show senescence and poor immunoregulation, making allogeneic UC-MSC stem cell therapy more effective.
Emerging evidence also supports MSC-derived exosomes (EVs) as a promising cell-free alternative. These nanosized vesicles carry miRNAs and proteins that suppress inflammation, enhance macrophage polarization to the M2 phenotype, and promote tissue repair.
CAR T-Cell Therapy
CAR T-cell therapy represents a breakthrough in immune-targeted cell therapy for refractory lupus. By engineering autologous T cells to recognize and eliminate CD19⁺ B cells, CAR T therapy disrupts the source of pathogenic autoantibodies.
Recent reports describe complete remission and drug-free disease control in severe SLE patients after CAR T infusion. However, the risk of cytokine release syndrome and treatment costs remain challenges for broader application.
Other Cellular Therapies
Emerging research explores the potential of several additional cell-based strategies:
- Regulatory T-cell (Treg) therapy: Restores immune tolerance by expanding CD4⁺CD25⁺FOXP3⁺ populations, reducing inflammatory cytokine production.
- Natural Killer (NK) cells: Offer selective targeting of autoreactive immune cells while sparing healthy tissues.
- Regulatory B cells (Bregs) and myeloid-derived suppressor cells (MDSCs): Exhibit IL-10–mediated immune suppression and have shown promise in preclinical lupus models.
- Dendritic cell (DC) immunotherapy and induced pluripotent stem cells (iPSCs) are being studied for personalized immune modulation and tissue regeneration.
Safety, Efficacy, and Outlook
Across clinical studies, stem cell therapy for systemic lupus erythematosus has shown strong safety and promising efficacy. MSC infusion, in particular, is non-myeloablative, avoids chemotherapy, and can be repeated as needed. While HSCT offers long-term immune reset, its risks restrict use to critical cases. In contrast, UC-MSC therapy provides a safer, regenerative alternative that can integrate with conventional lupus management.
Future directions include large-scale randomized trials, dose optimization, and combination therapies using MSC stem cell therapy -derived exosomes or engineered CAR-modified immune cells to maximize outcomes.
Conclusion
Cell-based regenerative approaches are reshaping the landscape of autoimmune disease management. For systemic lupus erythematosus, stem cell therapy especially umbilical cord MSC stem cell therapy shows significant potential to modulate immune imbalance, repair damaged tissues, and offer sustained remission. With ongoing advances in CAR T-cell therapy and MSC exosome technologies, the future of regenerative immunotherapy for lupus looks increasingly promising.
Keywords
Stem cell therapy for lupus, mesenchymal stem cell therapy, UC-MSC therapy, systemic lupus erythematosus treatment, regenerative immunotherapy, CAR T-cell therapy, hematopoietic stem cell transplantation, exosome therapy, cell therapy for autoimmune disease, Vega Stem Cell.
References
- Dao L.T.M. et al. Current Cell Therapies for Systemic Lupus Erythematosus. Stem Cells Translational Medicine.2024;13(9):859–872
- Sun L. et al. “Umbilical Cord Mesenchymal Stem Cell Transplantation in Severe and Refractory SLE.” Arthritis Rheum. 2010.
- Mackensen A. et al. “Anti-CD19 CAR T-Cell Therapy for Refractory SLE.” Nat Med. 2022.
- Yuan X. et al. “MSC Therapy Induces FLT3L and CD1c⁺ Dendritic Cells in SLE Patients.” Nat Commun. 2019.
Li A. et al. “Mesenchymal Stem Cell Therapy: Hope for Patients with Systemic Lupus Erythematosus.” Front Immunol. 2021.