Therapeutic Applications of Mesenchymal Stem Cells for Systemic Lupus Erythematosus
Mesenchymal stem cells (MSCs) have been intensively studied and applied in regenerative medicine and tissue engineering. Recently, their immune modulation functions make them as attractive potential approaches for autoimmune disease treatment. Systemic lupus erythematosus (SLE) is one type of chronic autoimmune diseases with multi-organ damaged by the immune system. Although current available treatments are effective for some patients, others are refractory for these therapies. The immuno-modulatory and regenerative characteristics of MSCs make them as one promising candidate for treating SLE. Thus, we would discuss their immune modulation effects, pre-clinical and clinical applications, and the potentials for immune tolerance re-establishment in SLE here.
KeywordsAutoimmune diseases Mesenchymal stem cells MSCs SLE Systemic lupus erythematosus
B cell activating factor
regulatory B cell
C-C motif chemokine ligand 2
hematopoietic stem cells
inducible nitric oxide synthase
mesenchymal stem cells
olfactory 1/early B cell factor-associated zinc-finger protein
systemic lupus erythematosus
follicular helper cell
transforming growth factor beta
T helper cells
tumor necrosis factor alpha
regulatory T cells
This work was supported by Natural Science Foundation of SZU (2017083), Natural Science Foundation of Shenzhen (JCYJ20170302152735071) and Medical Foundation of Guangdong (A2018308).
Conflict of Interest
The authors declare no commercial or financial conflict of interest.
The authors declare that this article does not contain any studies with human participants or animals.
- Banchereau R et al (2017) Understanding human autoimmunity and autoinflammation through transcriptomics. Annu Rev Immunol 35:337–370. https://doi.org/10.1146/annurev-immunol-051116-052225CrossRefPubMedPubMedCentralGoogle Scholar
- Choi EW et al (2012) Reversal of serologic, immunologic, and histologic dysfunction in mice with systemic lupus erythematosus by long-term serial adipose tissue-derived mesenchymal stem cell transplantation. Arthritis Rheum 64(1):243–253. https://doi.org/10.1002/art.33313CrossRefPubMedGoogle Scholar
- Contreras-Kallens P et al (2017) Mesenchymal stem cells and their immunosuppressive role in transplantation tolerance. Ann N Y Acad Sci. https://doi.org/10.1111/nyas.13364
- Feng X et al (2014) Restored immunosuppressive effect of mesenchymal stem cells on B cells after olfactory 1/early B cell factor-associated zinc-finger protein down-regulation in patients with systemic lupus erythematosus. Arthritis Rheumatol 66(12):3413–3423. https://doi.org/10.1002/art.38879CrossRefPubMedGoogle Scholar
- Gao L et al (2016) Phase II multicenter, randomized, double-blind controlled study of efficacy and safety of umbilical cord-derived mesenchymal stromal cells in the prophylaxis of chronic graft-versus-host disease after HLA-Haploidentical stem-cell transplantation. J Clin Oncol 34(24):2843–2850. https://doi.org/10.1200/JCO.2015.65.3642CrossRefPubMedGoogle Scholar
- Gao L et al (2017) Bone marrow-derived mesenchymal stem cells from patients with systemic lupus erythematosus have a senescence-associated secretory phenotype mediated by a mitochondrial antiviral signaling protein-interferon-beta feedback loop. Arthritis Rheumatol 69(8):1623–1635. https://doi.org/10.1002/art.40142CrossRefPubMedPubMedCentralGoogle Scholar
- Park MJ et al (2015) Adipose tissue-derived mesenchymal stem cells induce expansion of interleukin-10-producing regulatory B cells and ameliorate autoimmunity in a murine model of systemic lupus erythematosus. Cell Transplant 24(11):2367–2377. https://doi.org/10.3727/096368914X685645CrossRefPubMedGoogle Scholar
- Wang Q et al (2015) Combined transplantation of autologous hematopoietic stem cells and allogenic mesenchymal stem cells increases T regulatory cells in systemic lupus erythematosus with refractory lupus nephritis and leukopenia. Lupus 24(11):1221–1226. https://doi.org/10.1177/0961203315583541CrossRefPubMedGoogle Scholar
- Wang D et al (2017c) Serum IFN-gamma predicts the therapeutic effect of mesenchymal stem cells transplantation in systemic lupus erythematosus patients. Stem Cells Transl Med. https://doi.org/10.1002/sctm.17-0002
- Zhang Y et al (2014) Transplantation of umbilical cord mesenchymal stem cells alleviates pneumonitis of MRL/lpr mice. J Thorac Dis 6(2):109–117. https://doi.org/10.3978/j.issn.2072-1439.2013.12.48CrossRefPubMedPubMedCentralGoogle Scholar