scholarly journals Induction of Regulatory B-Cells by Mesenchymal Stem Cells is Affected by SDF-1α-CXCR7

2015 ◽  
Vol 37 (1) ◽  
pp. 117-130 ◽  
Author(s):  
Yan Qin ◽  
Zhihua Zhou ◽  
Fang Zhang ◽  
Yong Wang ◽  
Bing Shen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
B Cells ◽  
Immunomodulatory Effect ◽  
Regulatory Function ◽  
Mouse Bone Marrow ◽  
Regulatory B Cells ◽  
Paracrine Factors ◽  
Differentiation Potential ◽  
High Concentrations

Background/Aims: Mesenchymal stem cells (MSCs) possess immunomodulatory properties on a diverse array of immune cell lineages, including regulatory T and B cells (Tregs and Bregs, respectively). However, their specific effects and mechanisms underlying induction of Bregs remain unclear. The immune regulatory function of MSCs is exerted through both cell-cell contact and the release of soluble factors. The main objective of this study was to examine the role of the SDF-1-CXCR4/CXCR7 axis in the secretory action of MSCs, and potential effects on the immunoregulatory function of these cells. Methods: MSCs were isolated from mouse bone marrow and characterized according to their multilineage differentiation potential and their surface antigen expression. CD19+ B cells purified from mice splenocytes were co-cultured with MSCs at various ratios in the presence of LPS and αCD40. After 4 days, intracellular IL-10 production and cell surface CD1d and CD5 expression by CD19+ B cells were determined using flow cytometry, and the secretion of IL-10, IL-6, IgM, and IgG were assessed with ELISA. MSCs were treated with different concentrations of stromal derived factor-1α (SDF-1α) stimuli or transiently overexpressed with CXCR7. and their cell viability and immune regulatory effects of MSCs on Bregs were assessed. Results: MSCs induced IL-10-producing regulatory B cells and primarily stimulated the CD1d+CD5+B cell subset of IL-10+Breg cells to express IL-10. IL-10, IL-6, and IgM secretion were additionally induced by MSCs. The CXCR7 pathway was required for MSC viability and the production of paracrine factors under SDF-1α culture condition. Low concentrations of SDF-1α promoted the immunomodulatory effect of MSCs, leading to a further increase in IL-10-producing regulatory B cells and IL-10 secretion. In contrast, high concentrations of SDF-1α inhibited MSCs induction of IL-10+Breg cells. Notably, CXCR7 overexpression in MSCs reversed the inhibitory effect of high concentrations of SDF-1α and promoted the immunomodulatory effect of these cells. Conclusion: MSCs induce IL-10+Breg cells, which contribute to the generation of an immunosuppressive environment. SDF-1α and its receptor, CXCR7 play important roles in the immunomodulatory function of MSCs by regulating their paracrine actions.

scholarly journals Human Adipose Tissue-Derived Mesenchymal Stem Cells Abrogate Plasmablast Formation and Induce Regulatory B Cells Independently of T Helper Cells

Stem Cells ◽  
2015 ◽  
Vol 33 (3) ◽  
pp. 880-891 ◽  
Author(s):  
M. Franquesa ◽  
F. K. Mensah ◽  
R. Huizinga ◽  
T. Strini ◽  
L. Boon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Adipose Tissue ◽  
B Cells ◽  
T Helper Cells ◽  
Human Adipose Tissue ◽  
Regulatory B Cells ◽  
T Helper ◽  
Helper Cells

scholarly journals Immune Suppressive Effects of Tonsil-Derived Mesenchymal Stem Cells on Mouse Bone-Marrow-Derived Dendritic Cells

2015 ◽  
Vol 2015 ◽  
pp. 1-12 ◽  
Author(s):  
Minhwa Park ◽  
Yu-Hee Kim ◽  
Jung-Hwa Ryu ◽  
So-Youn Woo ◽  
Kyung-Ha Ryu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Dendritic Cells ◽  
T Cell ◽  
Cell Therapy ◽  
T Cell Subsets ◽  
Regulatory Function ◽  
Mouse Bone Marrow ◽  
And Function

Mesenchymal stem cells (MSCs) are considered valuable sources for cell therapy because of their immune regulatory function. Here, we investigated the effects of tonsil-derived MSCs (T-MSCs) on the differentiation, maturation, and function of dendritic cells (DCs). We examined the effect of T-MSCs on differentiation and maturation of bone-marrow- (BM-) derived monocytes into DCs and we found suppressive effect of T-MSCs on DCs via direct contact as well as soluble mediators. Moreover, T cell proliferation, normally increased in the presence of DCs, was inhibited by T-MSCs. Differentiation of CD4+T cell subsets by the DC-T cell interaction also was inhibited by T-MSCs. The soluble mediators suppressed by T-MSCs were granulocyte-macrophage colony-stimulating factor (GM-CSF), RANTES, interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1). Taken together, T-MSCs exert immune modulatory function via suppression of the differentiation, maturation, and function of BM-derived DCs. Our data suggests that T-MSCs could be used as a novel source of stem cell therapy as immune modulators.

scholarly journals Immunomodulatory Effect of Mesenchymal Stem Cells on B Cells

2012 ◽  
Vol 3 ◽  
Author(s):  
Marcella Franquesa ◽  
M. J. Hoogduijn ◽  
O. Bestard ◽  
J. M. Grinyó
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
B Cells ◽  
Immunomodulatory Effect

Overexpression of miR-126 promotes the differentiation of mesenchymal stem cells toward endothelial cells via activation of PI3K/Akt and MAPK/ERK pathways and release of paracrine factors

2013 ◽  
Vol 394 (9) ◽  
pp. 1223-1233 ◽  
Author(s):  
Feng Huang ◽  
Zhen-fei Fang ◽  
Xin-qun Hu ◽  
Liang Tang ◽  
Sheng-hua Zhou ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Culture Medium ◽  
Control Group ◽  
Mouse Bone Marrow ◽  
Negative Regulators ◽  
Paracrine Factors ◽  
Differentiated Cells ◽  
Erk1 Protein ◽  
Endothelial Lineage

Abstract The endothelial cell (EC)-specific miRNA, miR-126, is known to promote angiogenesis in response to angiogenic factors by repressing negative regulators of signal transduction pathways; however, whether miR-126 might regulate the differentiation of stem cells toward endothelial lineage remains unknown. To answer this question, in this study mesenchymal stem cells (MSCs) harvested from C57BL/6 mouse bone marrow were transfected with miR-126 (MSCmiR-126) using recombinant lentiviral vectors. Results showed the para-secretion and the expression levels of phosphorylated PI3K p85, Akt, p38, ERK1 protein in the MSCmiR-126 group were dramatically increased when compared with the control group. With half culture medium refreshed every 3 days, a small number of 6-day-cultured MSCmiR-126 differentiated into endothelial-like cells and most of 9-day-cultured MSCmiR-126 formed a cobblestone-like structure. These differentiated cells evidently expressed EC-specific makers and possessed mature ECs function, while inhibition of paracrine factors suppressed the MSC-EC differentiation. Strikingly, the increased secretion of MSCmiR-126 and their endothelial-differentiated potential were deprived by using a PI3K or MEK chemical inhibitor. Our results suggest that overexpression of miR-126 agumenting the endothelial differentiation of MSCs might in part be attributable to the activation of PI3K/Akt and MAPK/ERK pathways and an increased release of paracrine factors.

scholarly journals Effect of Serum and Oxygen Concentration on Gene Expression and Secretion of Paracrine Factors by Mesenchymal Stem Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Patrick Page ◽  
Joshua DeJong ◽  
Alaina Bandstra ◽  
Robert A. Boomsma
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Culture Media ◽  
Coronary Artery Occlusion ◽  
Serum Levels ◽  
Matrix Metalloproteinase 2 ◽  
Mouse Bone Marrow ◽  
Paracrine Factors

Mesenchymal stem cells (MSC) secrete paracrine factors that may exert a protective effect on the heart after coronary artery occlusion. This study was done to determine the effect of hypoxia and serum levels on the mRNA expression and secretion of paracrine factors. Mouse bone marrow MSC were cultured with 5% or 20% serum and in either normoxic (21% O2) or hypoxic (1% O2) conditions. Expression of mRNA for vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1α(MIP-1α), MIP-1β, and matrix metalloproteinase-2 (MMP-2) was determined by RT-qPCR. Secretion into the culture media was determined by ELISA. Hypoxia caused a reduction in gene expression for MCP-1 and an increase for VEGF (5% serum), MIP-1α, MIP-1β, and MMP-2. Serum reduction lowered gene expression for VEGF (normoxia), MCP-1 (hypoxia), MIP-1α(hypoxia), MIP-1β(hypoxia), and MMP-2 (hypoxia) and increased gene expression for MMP-2 (normoxia). The level of secretion of these factors into the media generally paralleled gene expression with some exceptions. These data demonstrate that serum and oxygen levels have a significant effect on the gene expression and secretion of paracrine factors by MSC which will affect how MSC interactin vivoduring myocardial ischemia.

scholarly journals Differentiation and Molecular Properties of Mesenchymal Stem Cells Derived from Murine Induced Pluripotent Stem Cells Derived on Gelatin or Collagen

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Chizuka Obara ◽  
Kazuya Takizawa ◽  
Kenichi Tomiyama ◽  
Masaharu Hazawa ◽  
Ai Saotome-Nakamura ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Molecular Properties ◽  
Mouse Bone Marrow ◽  
Step Method ◽  
Differentiation Potential ◽  
Extracellular Matrix Components ◽  
Primary Mouse ◽  
Adipose Differentiation ◽  
Coated Surfaces

The generation of induced-pluripotential stem cells- (iPSCs-) derived mesenchymal stem cells (iMSCs) is an attractive and promising approach for preparing large, uniform batches of applicable MSCs that can serve as an alternative cell source of primary MSCs. Appropriate culture surfaces may influence their growth and differentiation potentials during iMSC derivation. The present study compared molecular properties and differentiation potential of derived mouse iPS-MSCs by deriving on gelatin or collagen-coated surfaces. The cells were derived by a one-step method and expressed CD73 and CD90, but CD105 was downregulated in iMSCs cultured only on gelatin-coated plates with increasing numbers of passages. A pairwise scatter analysis revealed similar expression of MSC-specific genes in iMSCs derived on gelatin and on collagen surfaces as well as in primary mouse bone marrow MSCs. Deriving iMSCs on gelatin and collagen dictated their osteogenic and adipose differentiation potentials, respectively. Derived iMSCs on gelatin upregulatedBmp2andLifprior to induction of osteogenic or adipose differentiation, while PPARγwas upregulated by deriving on collagen. Our results suggest that extracellular matrix components such as gelatin biases generated iMSC differentiation potential towards adipose or bone tissue in their derivation process via up- or downregulation of these master genes.

scholarly journals Comparative Study on In Vitro Culture of Mouse Bone Marrow Mesenchymal Stem Cells

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Yuxin Hu ◽  
Bin Lou ◽  
Xiafang Wu ◽  
Ruirui Wu ◽  
Huihui Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Adipogenic Differentiation ◽  
Culture Method ◽  
Culture Conditions ◽  
Mouse Bone Marrow ◽  
Differentiation Potential ◽  
Initial Medium

In vitro culture of mesenchymal stem cells (MSCs) from mouse bone marrow (BM) has been hampered because of the low yield of MSCs during isolation and the contamination of hematopoietic cells during expansion. The lack of specific mouse BM-MSC markers increases the difficulty. Several techniques have been reported to improve the purity and in vitro growth of mouse BM-MSCs. However, systematic report on comparison of characteristics in primary BM-MSCs between different culture conditions is rare. Here, we studied the effects of oxygen concentrations and initial medium replacement intervals, along with cell passages, on mouse BM-MSCs isolated with differential adhesion method. BM-MSCs exhibited elevated proliferative and clonogenic abilities in 5% oxygen compared with 10% and 21% oxygen, as well as a better expression of the MSC marker Sca-1. Adipogenic and osteogenetic differentiation of BM-MSCs can be observed in both 21% and 5% oxygen. Adipogenic differentiation appeared stronger under normoxia conditions. BM-MSCs showed increased proliferative capacity and adipogenic/osteogenetic differentiation potential when initial medium replacement interval was 4 days compared with 1 day. As passage number increased, cells were more MSC-like in morphology and in expression of surface markers (positive for CD29, CD44, and Sca-1 and negative for CD11b, CD19, and CD45). These data provide new insight into optimizing the culture method and understanding the biological characteristics of mouse BM-MSCs during in vitro expansion.

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