Zhonghua Nei Ke Za Zhi. 2007 Dec;46(12):1018-2
Authors: Sun Y, Zhang FS, Zhang ZY
OBJECTIVE: To study the in vitro modulation of autogeneic and allogenic regulatory T lymphocytes proliferation by bone marrow mesenchymal stem cells (MSCs) in patients with systemic lupus erythematosis (SLE). METHODS: Human MSCs were separated with Percoll (1.073 g/ml) from bone marrow of patients with SLE or healthy subjects. The purity of MSCs was identified with the phenotypes by fluorescence active cell sorter (FACS). The subset regulatory T cells in the peripheral blood of patients with SLE were isolated with magnetic activated cell sorting (MACS) CD4 and CD25 microbeads. Lymphocytes or CD4+ CD25+ T cells isolated from the peripheral blood of SLE patients were cocultured either with autologous MSCs or MSCs from healty donors. The proliferation activities of lymphocytes and CD4+ CD25+ T cells were investigated with methyl thiazolyl tetrazolium( MTr) test. The level of IL-10 and transforming growth factor beta (TGFbeta) was determined with enzyme-linked immunosorbent assay (ELISA). RESULTS: The lymphocyte activity in SLE was suppressed by autogeneic and allogeneic MSCs and the inhibition rate was 56.32% and 65.46%, respectively. A stronger immunosuppressive effect of allogeneic MSCs was detected. MSCs were capable of increasing the proportion of allogeneic and autogeneic regulatory T cells in a dose dependent fashion. MSCs stimulated CD4+ CD25+ T cells to produce IL-10 and TGFbeta. CONCLUSION: MSCs can suppress lymphocyte proliferation and increase CD4+ CD25+ T cells. MSCs might play important roles in immunosuppressant lymphocyte proliferation and be important to cooperate with autogeneic hematopoietic stem cells in transplantation.
PMID: 18478921 [PubMed – indexed for MEDLINE]
Allogeneic adipose-derived stem cells suppress Th17 lymphocytes in patients with active lupus in vitro.
Acta Biochim Biophys Sin (Shanghai). 2011 Oct;43(10):805-12. doi: 10.1093/abbs/gmr077. Epub 2011 Sep 7. Lai K1, Zeng K, Zeng F, Wei J, Tan G.
Interleukin-17 (IL-17)-producing CD4(+) T cells (Th17 cells) have been proven to play a critical role in the pathogenesis of systemic lupus erythematosus (SLE). To shed light on the mechanism of immunoregulation of adipose-derived stem cells (ADSCs), we investigated the effects of allogeneic ADSCs on the Th17 lymphocytes of patients with active SLE by co-culturing ADSCs and peripheral blood mononuclear cells of these patients in vitro. The results indicated that ADSCs from passage 3 (P3) down-regulated the proportion of Th17 cells and their abilities to produce IL-17, whereas ADSCs from passage 8 (P8) had contrasting effect. The results also showed cell-cell contact played a role in P3 down-regulation. Blocking the functional pathway of IL-23 (both its ligand and its receptor) also contributed to this suppression. These results suggested that immunomodulation of ADSCs may be achieved by partially suppressing the number and capability of Th17 lymphocytes, indicating that ADSCs could be employed as therapeutic tools for the autoimmune diseases.
Transplantation of Adipose Tissue-Derived Mesenchymal Stem Cells Prevents the Development of Lupus Dermatitis.
Stem Cells Dev. 2015 Sep 1;24(17):2041-51. doi: 10.1089/scd.2015.0021. Epub 2015 Jun 17.
Choi EW1,2, Shin IS3, Song JW1, Yun TW1, Yang J1,2, Choi KS1,2, Seong JK4.
MRL/lpr mice spontaneously develop high titers of anti-dsDNA antibodies and symptoms such as glomerular nephritis and organ weight gain. They also develop spontaneous skin inflammation similar to the cutaneous lesions common in human lupus erythematosus. This study aimed to compare the effects of long-term serial administration of human adipose tissue-derived mesenchymal stem cells (ASCs), CTLA4Ig-overexpressing ASCs, and cyclophosphamide treatment in MRL/lpr mice. MRL/lpr mice were divided into saline (C), cyclophosphamide (Y), ASC early (E), ASC late (L), and CTLA4Ig-overexpressing ASC (CT) treatment groups. Background-matched control MRL/MPJ mice treated with saline (N) were also compared. The treatment period was 5-23 weeks, except for the L group (15-23 weeks). Blood and tissue samples were collected when the mice were 24 weeks old. Organ weight, anti-dsDNA antibodies, urine protein, skin and kidney histologic abnormalities, and trabecular bone volume were evaluated. The Y group showed the greatest decrease in anti-dsDNA antibodies, organ weight, degree of kidney inflammation and glomerular infiltration of C3, and incidence rate of severe proteinuria; the E, L, and CT treatment groups showed better results than the C group. ASC transplantation reduced anti-dsDNA antibody levels significantly. Mice treated with ASCs or CTLA4Ig-ASCs starting from the early disease stage did not show dermatitis upon gross examination; they demonstrated significant improvement in hyperkeratosis, acanthosis, and inflammatory cell infiltration scores in histopathology. Micro-CT analysis revealed that cyclophosphamide treatment significantly decreased bone volume and increased bone spacing in the trabecular bone. Thus, we found that ASC and CTLA4-ASC treatments prevent lupus dermatitis development in MRL/lpr mice without adverse effects.