Liang et al. Ann Rheum Dis. 2010 Aug;69(8):1423-9.
Mesenchymal stem cells are unique in that on the one hand they are capable of differentiating into a variety of tissues, but on the other hand they also are potently anti-inflammatory and immune modulatory.
Evidence of immune modulation comes from studies that show mesenchymal stem cells: a) directly suppress ongoing mixed lymphocyte reaction; b) produce immune suppressive cytokines such as IL-10; c) produce immune suppressive enzymes such as indolamine 2,3 deoxygenase; d) inhibit natural killer and CD8 cytotoxic T cell activity; e) inhibit dendritic cell maturation; and f) stimulate production of T regulatory cells.
Animal studies covered on our youtube channel www.youtube.com/cellmedicine have shown that mesenchymal stem cells inhibit collagen induced arthritis and experimental allergic encephalomyelitis, which represent human rheumatoid arthritis and multiple sclerosis, respectively.
Since these cells are such potent immune modulators, they have been used with some success in the treatment of immunological diseases such as graft versus host disease (GVHD). Medistem and Cellmedicine have previously used fat derived stem cells, which contain high concentrations of mesenchymal stem cells, in order to treat rheumatoid arthritis. In the current paper mesenchymal stem cells from the bone marrow where used to treat the autoimmune disease systemic lupus erythematosus.
Scientists at the Department of Rheumatology and Immunology, The Affiliated Drum Tower Hospital of Nanjing University Medical School, in Nanjing, China, reported a clinical trial of allogeneic (universal donor) mesenchymal stem cells in the treatment of patients with treatment-refractory systemic lupus erythematosus (SLE).
Fifteen patients with SLE who did not respond to conventional treatments where administered bone marrow derived mesenchymal stem cells isolated from allogeneic donors. No chemotherapy or immune suppression was used. Administration of stem cells was performed intravenously.
Mean patient follow up was 17.2+/-9.5 months with 13 patients have been followed for more than 12 months. 15/15 patients presented with clinical improvements subsequent to stem cell therapy. At 12-month follow-up, SLEDAI scores dropped from 12.2+/-3.3 to 3.2+/-2.8 and proteinuria decreased from 2505.0+/-1323.9 to 858.0+/-800.7 mg/24 h. At 1-year follow-up in 13 patients, 2 had a relapse of proteinuria, while the other 11 continue to have decreased disease activity on minimal treatment. Anti-dsDNA levels decreased. Improvement in glomerular filtration rate was noted in two patients in which formal testing was performed. Non-renal-related manifestations also improved significantly. No serious adverse events were reported.
This study demonstrated that mesenchymal stem cells are capable of not only inhibiting the pathological processes in SLE (eg production of anti-dsDNA antibodies) but also reversing renal damage that has occurred as a result of the disease process. The fact that some of the patients relapsed may mean that there is a rationale for multiple administration of mesenchymal stem cells.
