Mesenchymal stromal cells relieved systemic lupus erythematosus via CCL2 dependent macrophage polarization.

Safety and preliminary efficacy of allogeneic bone marrow-derived multipotent mesenchymal stromal cells for systemic sclerosis: a single-centre, open-label, dose-escalation, proof-of-concept, phase 1/2 study.

Historical Perspectives and Advances in Mesenchymal Stem Cell Research for the Treatment of Liver Diseases

The defective MEK/ERK signaling pathway and downstream hypomethylation pattern of lymphocytes are crucial for the pathogenesis of systemic lupus erythematosus (SLE). However, the role that the mesenchymal stem cells play in the MEK/ERK signaling pathway and DNA methylation of peripheral blood mononuclear cells (PBMC) from SLE patients remains unknown. In this study, we found that the MEK/ERK signaling pathway of PBMC from SLE patients was activated after the coculture with bone marrow-derived mesenchymal stem cells (BM-MSC) compared with that from the control group. In addition, the expression level of DNA methyltransferase 1 (DNMT1) increased while the levels of CD70, integrin, alpha L (ITGAL), selectin-l, and IL-13 were reduced in PBMC from SLE patients. However, no obvious effect of BM-MSC on PBMC from healthy controls was observed. These findings revealed that BM-MSC might downregulate the expression of methylation-sensitive genes and then suppress the autoactivated PBMC via the MEK/ERK signaling pathway. And it may be one of the mechanisms that BM-MSC ameliorated SLE.

Stem Cell Therapy for Liver Disease: Parameters Governing the Success of Using Bone Marrow Mesenchymal Stem Cells

BackgroundSystemic lupus erythematosus (SLE) is an autoimmune disease which has been described as a hematopoietic stem cell (HSC) disorder. Besides HSCs, bone marrow contains mesenchymal stem cells (MSCs) which is...

Human stromal (mesenchymal) stem cells (hMSC) represent a group of non-hematopoietic stem cells present in the bone marrow stroma and the stroma of other organs including subcutaneous adipose tissue, placenta, and muscles. They exhibit the characteristics of somatic stem cells of self-renewal and multi-lineage differentiation into mesoderm-type of cells, e.g., to osteoblasts, adipocytes, chondrocytes and possibly other cell types including hepatocytes and astrocytes. Due to their ease of culture and multipotentiality, hMSC are increasingly employed as a source for cells suitable for a number of clinical applications, e.g., non-healing bone fractures and defects and also non-skeletal degenerative diseases like heart failure. Currently, the numbers of clinical trials that employ MSC are increasing. However, several biological and biotechnological challenges need to be overcome to benefit from the full potential of hMSC. In this current review, we present some of the most important and recent advances in understanding of the biology of hMSC and their current and potential use in therapy.

Toward Brain Tumor Gene Therapy Using Multipotent Mesenchymal Stromal Cell Vectors

Toward an 'off the shelf' technology for burn victims: healing wounds with mesenchymal stem cells.

Aim Mesenchymal stem cells (MSCs) have potent immunosuppressive properties to control systemic lupus erythematosus (SLE) disease by inhibiting indoleamine 2,3-dioxygenase (IDO), and increasing regulatory T cells (Treg) to control innate and adaptive immune cells. However, the interaction and mechanism regarding IDO and B cells in the co-culture of MSC and SLE peripheral blood mononuclear cell (PBMCs) remain unclear. This study aimed to investigate the effects of MSCs in controlling B cells through IDO expression in PBMC of SLE patients. Methods This study used a post-test control group design. MSCs were obtained from human umbilical cord blood and characterized according to their surface antigen expression and multilineage differentiation capacities. PBMCs isolated from SLE patients were divided into five groups: sham, control, and three treatment groups. The treatment groups were treated by co-culturing MSCs to PBMCs with a ratio of 1:10, 1:25, and 1:40 for 72 h incubation. The B cell levels were analysed by flow cytometry with cytometric bead array (CBA) and the IDO levels were determined by ELISA. Results The percentages of B cells decreased significantly in groups treated by dose-dependent MSCs, particularly in T1 and T2 groups. These findings were aligned with the significant decrease of the IDO level. Conclusion MSCs control B cells-mediated by a decrease of IDO in PBMC of SLE patients.

Autologous bone marrow-derived mesenchymal stromal cell therapy with early tacrolimus withdrawal: The randomized prospective, single-center, open-label TRITON study

Decision letter: Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins

Editor's evaluation: Osteosarcoma-enriched transcripts paradoxically generate osteosarcoma-suppressing extracellular proteins

Reversing Acute Kidney Injury Using Pulsed Focused Ultrasound and MSC Therapy: A Role for HSP-Mediated PI3K/AKT Signaling

Recent studies indicate that cardiac transfer of adult stem cells can have a favorable impact on tissue perfusion and contractile performance of the infarcted heart. Several cell sources are being explored in an effort to regenerate infarcted myocardium, including hematopoietic stem cells, endothelial progenitor cells, cardiac resident stem cells, bone marrow–derived multipotent stem cells, and mesenchymal stem cells (MSCs). Each of these cell types may have its own profile of advantages, limitations, and practicability issues in specific settings. Studies comparing the regenerative capacity of distinct cell populations are scarce. Most clinical investigators have therefore chosen a pragmatic approach by using unselected bone marrow cells that contain different stem cell populations. Basic scientists, by contrast, are focusing more on specific cell populations in a quest to understand the biological foundations of cell therapy and to identify the most promising stem cells for cardiac regeneration.1 See p 214 MSCs are a rare population of self-renewing, multipotent cells present in adult bone marrow. Although MSCs represent <0.01% of all nucleated bone marrow cells, they can be readily expanded in vitro. In defined culture media, MSCs differentiate into several mesenchymal cell lineages, including cardiomyocytes.2,3 When injected into normal adult myocardium, MSCs differentiate into cardiomyocyte-like cells with sarcomeric organization.4 In an earlier study in pigs with myocardial infarction (MI), MSCs grafted into the infarcted area were shown to express muscle-specific markers and to improve regional wall motion.5 Ease of isolation, high expansion capability, and cardiomyogenic potential have led to the proposition that MSCs may be a good choice for cell-based therapies of MI.6 In a report published in this issue of Circulation , Dai et al7 have …

Objective To explore the effects of leptin on the senescence of bone marrow-derived mesenchymal stem cells, frequencies of Treg and Th17 cells, and lupus disease in MRL/lpr mice, and to explore the pathogenesis of systemic lupus erythematosus (SLE). Methods Leptin (1 μg/g) or phosphate buffer saline (PBS) was injected into C57BL/6 (B6) mice, ob/ob mice and MRL/lpr mice intra-peritoneally. Urine protein was examined by Coomassie brilliant blue method. The levels of serum leptin, antinuclear antibody (ANA), anti-dsDNA antibody and immunoglobulin (Ig)G were detected by enzyme linked immunosorbent assay (ELISA). Bone marrow derived mesenchymal stem cells (MSCs) were isolated, and treated with or without leptin, then the senescence of MSCs were evaluated by SA-β-gal staining, the levels of p53 and p21 mRNA were measured by real time polymerase chain reaction (PCR), the protein levels of p53 and p21 were tested by Western blotting method. Data were analyzed with t test and ANOVA. Results The level of serum leptin was higher in MRL/lpr mice than that of B6 mice [(4.5±0.8) ng/ml vs (2.3±0.5) ng/ml, t=2.38, P<0.05]. Leptin treatment in vivo accelerated the senescence of bone marrow-derived MSCs from all B6 mice, lupus mice and ob/ob mice, manifestedas increased frequencies of SA-β-gal positive cells [(20.6±0.6)% vs (15.4±1.6)%, t=8.09, P<0.05], higher levels of mRNA and p53 and p21 protein. Leptin treatment in vivo also down-regulated the frequency of Treg cells [(2.77±0.23)% vs (5.01±0.18)% t=3.91, P<0.01], and up-regulated Th17 cells [(2.24±0.11)% vs (1.74±0.07)%, t=5.013, P<0.01]. The titer of ANA was further increased in leptin-treated MRL/lpr mice [(288±69) U/ml vs (190±90) U/ml, t=2.84, P<0.05]. The levels of serum anti-dsDNA antibody were also remarkably elevated [(12 399±1 237) U/ml vs (6 217±1 304) U/ml, t=3.44, P<0.01]. Leptin could increase the secretion of total IgG [MRL/lpr (27.2±2.9) mg/ml vs (25.0±3.3) mg/ml, t=3.07, P<0.05]. The proteinuria concentration was increased in lupus mice [(1.00±0.10) mg/ml vs (0.81±0.06) mg/ml, t=3.31, P<0.05], demonstrating that leptin accelerates lupus nephritis. Conclusion Leptin administr-ation in vivo enhances the senescence of bone marrow derived MSCs, dysregulate of Treg/Th17 cells from MRL/lpr mice, which impaires the role of immuno-modulation, and aggravates the progress of lupus disease. Key words: Leptin; Lupus erythematosus, systemic; Cell senescence; Mesenchymal stem cell; Immune regulation