scholarly journals Multiple Functions of MSCA-1/TNAP in Adult Mesenchymal Progenitor/Stromal Cells

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
David Estève ◽  
Jean Galitzky ◽  
Anne Bouloumié ◽  
Caroline Fonta ◽  
René Buchet ◽  
...  
Keyword(s):  
Stem Cells ◽  
Alkaline Phosphatase ◽  
Mesenchymal Stem Cells ◽  
Stromal Cells ◽  
Proof Of Concept ◽  
Wide Range ◽  
Semantic Shift ◽  
Definition Of ◽  
Different Tissues

Our knowledge about mesenchymal stem cells has considerably grown in the last years. Since the proof of concept of the existence of such cells in the 70s by Friedenstein et al., a growing mass of reports were conducted for a better definition of these cells and for the reevaluation from the term “mesenchymal stem cells” to the term “mesenchymal stromal cells (MSCs).” Being more than a semantic shift, concepts behind this new terminology reveal the complexity and the heterogeneity of the cells grouped in MSC family especially as these cells are present in nearly all adult tissues. Recently, mesenchymal stromal cell antigen-1 (MSCA-1)/tissue nonspecific alkaline phosphatase (TNAP) was described as a new cell surface marker of MSCs from different tissues. The alkaline phosphatase activity of this protein could be involved in wide range of MSC features described below from cell differentiation to immunomodulatory properties, as well as occurrence of pathologies. The present review aims to decipher and summarize the role of TNAP in progenitor cells from different tissues focusing preferentially on brain, bone marrow, and adipose tissue.

scholarly journals Single-cell Transcriptomic Analysis Reveals the Cellular Heterogeneity of Mesenchymal Stem Cells

2021 ◽  
Author(s):  
Chen Zhang ◽  
Xueshuai Han ◽  
Jingkun Liu ◽  
Lei Chen ◽  
Ying Lei ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Single Cell ◽  
Ex Vivo ◽  
Developmental Trajectory ◽  
Cellular Heterogeneity ◽  
Multipotent Progenitor Cells ◽  
Definition Of

Ex vivo-expanded mesenchymal stem cells (MSCs) have been demonstrated to be a heterogeneous mixture of cells exhibiting varying proliferative, multipotential, and immunomodulatory capacities. However, the exact characteristics of MSCs remain largely unknown. By single-cell RNA sequencing of 61,296 MSCs derived from bone marrow and Wharton's jelly, we revealed five distinct subpopulations. The developmental trajectory of these five MSC subpopulations were mapped, revealing a differentiation path from stem-like active proliferative cells (APCs) to multipotent progenitor cells, followed by the branching into two paths - adipogenesis or osteochondrogenesis - and subsequent differentiation into unipotent prechondrocytes. The stem-like APCs, expressing the perivascular mesodermal progenitor markers CSPG4/MCAM/NES, uniquely exhibited strong proliferation and stemness signatures. Remarkably, the prechondrocyte subpopulation specifically expressed immunomodulatory genes and was able to suppress activated CD3+ T cell proliferation in vitro, supporting the role of this population in immunoregulation. In summary, our analysis mapped the heterogeneous subpopulations of MSCs and identified two subpopulations with potential functions in self-renewal and immunoregulation. Our findings advance the definition of MSCs by identifying the specific functions of its heterogeneous cellular composition, allowing for more specific and effective MSC application through the purification of its functional subpopulations.

Genomic and Proteomic Signatures of Human Mesenchymal Stem Cells.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2300-2300
Author(s):  
Wolfgang Wagner ◽  
Robert E. Feldmann ◽  
Frederik Wein ◽  
Anja Seckinger ◽  
Ulf Krause ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Culture Conditions ◽  
Clinical Applications ◽  
Differentially Expressed ◽  
Cdna Clones ◽  
Reference Map ◽  
Definition Of ◽  
Different Tissues

Abstract Mesenchymal stem cells (MSC) raise high hopes in clinical applications. However, the lack of common standards and a precise definition of MSC preparations remains a major obstacle in research and application of MSC. Whereas surface antigen markers have failed to precisely define this population, a combination of proteomic data and microarray data provides a new dimension for the definition of MSC preparations. To define the molecular signatures at a genomic and proteomic level we have compared the MSC preparations isolated from different sources (adipose tissue, bone marrow and umbilical cord blood) from different donors, as well as from the same donor cultured under different conditions. As a references we have used non-multipotent human fibroblasts (HS68 and NHDF). No phenotypic differences were observed between MSC and fibroblasts by flow cytometry using a panel of 22 surface antigen markers. Gene expression profiles were compared by cDNA microarray analysis (51,144 different cDNA clones of the RZPD3 Unigene Set). Twenty-five genes were overlapping more than two-fold up-regulated in all MSC preparations and these included fibronectin, ECM2, glypican-4, ID1, NF1B, HOXA5 and HOXB6 whereas several inhibitors of the Wnt-pathway (DKK1, DKK3, SFRP1) were higher expressed in fibroblasts. Differential gene expression was verified for 20 genes by RT-PCR. Hierarchical cluster analysis revealed a correlation of four individual donor samples for each MSC preparation while pair wise comparison of MSC from different tissues or culture-isolation procedures revealed between 206 to 1113 differentially expressed ESTs (p<0.001). Using two-dimensional gel electrophoresis and mass spectometry we have generated a proteome reference map of MSC. 136 protein spots were unambiguously identified most of which play a role in cytoskeleton, protein folding and metabolism. This reference map was used to compare protein expression of MSC isolated under different culture conditions. Corresponding cDNA clones were then selected on our microarray. Combination of datasets revealed that genes that were differentially expressed on mRNA level (p<0.05) were differentially expressed on protein level as well (Pearson correlation = 0.83). Interchanging culture conditions revealed that differential expression was directly regulated by medium in some genes whereas it remained constant in others. Expressions of fibronectin, vimentin, myosin, tropomyosin and ezrin were analyzed by fluorescence microscopy whereby no subpopulations could be discriminated within cell preparations while marked differences were observed in morphology and organization of MSC isolated under different culture conditions. Our results provide evidence for reproducible isolation of similar and homogeneous MSC preparations under standardized isolation conditions, while MSC from different tissues or culture conditions display significant differences in their transcriptome, proteome and cellular organization. Our comparative approach provides foundation for a reliable quality control using genotypic and proteomic analysis for clinical applications.

scholarly journals Mesenchymal Stem Cells in Perichondrium Express Activated Leukocyte Cell Adhesion Molecule and Participate in Bone Marrow Formation

2002 ◽  
Vol 195 (12) ◽  
pp. 1549-1563 ◽  
Author(s):  
Fumio Arai ◽  
Osamu Ohneda ◽  
Takeshi Miyamoto ◽  
Xiu Qin Zhang ◽  
Toshio Suda
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Cell Adhesion ◽  
Adhesion Molecule ◽  
Stromal Cells ◽  
Bone Marrow Stromal Cells ◽  
Cell Adhesion Molecule ◽  
Hematopoietic Bone Marrow

Perichondrium in fetal limb is composed of undifferentiated mesenchymal cells. However, the multipotency of cells in this region and the role of perichondrium in bone marrow formation are not well understood. In this report, we purified and characterized perichondrial cells using a monoclonal antibody against activated leukocyte cell adhesion molecule (ALCAM) and investigated the role of perichondrial cells in hematopoietic bone marrow formation. ALCAM is expressed on hematopoietic cells, endothelial cells, bone marrow stromal cells, and mesenchymal stem cells and mediates homophilic (ALCAM–ALCAM)/heterophilic (ALCAM-CD6) cell adhesion. Here we show by immunohistochemical staining that ALCAM is expressed in perichondrium. ALCAM+ perichondrial cells isolated by FACS® exhibit the characteristics of mesenchymal stem cells. ALCAM+ cells can differentiate into osteoblasts, adipocytes, chondrocytes, and stromal cells, which can support osteoclastogenesis, hematopoiesis, and angiogenesis. Furthermore, the addition of ALCAM-Fc or CD6-Fc to the metatarsal culture, the invasion of the blood vessels to a cartilage was inhibited. Our findings indicate that ALCAM+ perichondrial cells participate in vascular invasion by recruiting osteoclasts and vessels. These findings suggest that perichondrium might serve as a stem cell reservoir and play an important role in the early development of a bone and bone marrow.

scholarly journals Role of 1,25-Dihydroxyvitamin D3 on Osteogenic Differentiation and Mineralization of Chicken Mesenchymal Stem Cells

2021 ◽  
Vol 12 ◽  
Author(s):  
Chongxiao Chen ◽  
Roshan Adhikari ◽  
Dima Lynn White ◽  
Woo Kyun Kim
Keyword(s):  
Stem Cells ◽  
Alkaline Phosphatase ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Mrna Expression ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Cell Stage ◽  
Dihydroxyvitamin D3

1,25-dihydroxyvitamin D3 (1,25OHD) has been suggested to play an important role in osteogenic differentiation and mineralization. However, limited data have been reported in avian species. In the present study, the direct role of 1,25OHD on osteogenic differentiation and mineralization in chicken mesenchymal stem cells (cMSCs) derived from day-old broiler bones was investigated. cMSCs were treated with control media (C), osteogenesis media (OM), OM with 1, 5, 10, and 50 nM 1,25OHD, respectively. The messenger RNA (mRNA) samples were obtained at 24 and 48 h and 3 and 7 days to examine mRNA expression of key osteogenic genes [runt related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2), collagen type I alpha 2 chain (COL1A2), bone gamma-carboxyglutamate protein (BGLAP), secreted phosphoprotein 1 (SPP1), and alkaline phosphatase (ALP)]. Cells were stained at 7, 14, and 21 days using Von Kossa (mineralization), Alizarin Red (AR; mineralization), and Alkaline Phosphatase (early marker) staining methods. From the mRNA expression results, we found a time-dependent manner of 1,25OHD on osteoblast differentiation and mineralization. In general, it showed an inhibitory effect on differentiation and mineralization during the early stage (24 and 48 h), and a stimulatory effect during the late cell stage (3 and 7 days). The staining showed 1,25OHD had an inhibitory effect on ALP enzyme activities and mineralization in a dosage-dependent manner up to 14 days. However, at 21 days, there was no difference between the treatments. This study provides a novel understanding of the effects of 1,25OHD on osteogenic differentiation and mineralization of cMSCs depending on cell stage and maturity.

Overexpression of Pygo2 Increases Differentiation of Human Umbilical Cord Mesenchymal Stem Cells into Cardiomyocyte-like Cells

2020 ◽  
Vol 20 (4) ◽  
pp. 318-324 ◽  
Author(s):  
Lei Yang ◽  
Shuoji Zhu ◽  
Yongqing Li ◽  
Jian Zhuang ◽  
Jimei Chen ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Umbilical Cord ◽  
Heart Function ◽  
Critical Role ◽  
Human Umbilical Cord ◽  
Stem Cell Markers ◽  
Quantitative Real Time Pcr ◽  
Qrt Pcr

Background: Our previous studies have shown that Pygo (Pygopus) in Drosophila plays a critical role in adult heart function that is likely conserved in mammals. However, its role in the differentiation of human umbilical cord mesenchymal stem cells (hUC-MSCs) into cardiomyocytes remains unknown. Objective: To investigate the role of pygo2 in the differentiation of hUC-MSCs into cardiomyocytes. Methods: Third passage hUC-MSCs were divided into two groups: a p+ group infected with the GV492-pygo2 virus and a p− group infected with the GV492 virus. After infection and 3 or 21 days of incubation, Quantitative real-time PCR (qRT-PCR) was performed to detect pluripotency markers, including OCT-4 and SOX2. Nkx2.5, Gata-4 and cTnT were detected by immunofluorescence at 7, 14 and 21 days post-infection, respectively. Expression of cardiac-related genes—including Nkx2.5, Gata-4, TNNT2, MEF2c, ISL-1, FOXH1, KDR, αMHC and α-Actin—were analyzed by qRT-PCR following transfection with the virus at one, two and three weeks. Results : After three days of incubation, there were no significant changes in the expression of the pluripotency stem cell markers OCT-4 and SOX2 in the p+ group hUC-MSCs relative to controls (OCT-4: 1.03 ± 0.096 VS 1, P > 0.05, SOX2: 1.071 ± 0.189 VS 1, P > 0.05); however, after 21 days, significant decreases were observed (OCT-4: 0.164 ± 0.098 VS 1, P < 0.01, SOX2: 0.209 ± 0.109 VS 1, P < 0.001). Seven days following incubation, expression of mesoderm specialisation markers, such as Nkx2.5, Gata-4, MEF2c and KDR, were increased; at 14 days following incubation, expression of cardiac genes, such as Nkx2.5, Gata-4, TNNT2, MEF2c, ISL-1, FOXH1, KDR, αMHC and α-Actin, were significantly upregulated in the p+ group relative to the p− group (P < 0.05). Taken together, these findings suggest that overexpression of pygo2 results in more hUCMSCs gradually differentiating into cardiomyocyte-like cells. Conclusion: We are the first to show that overexpression of pygo2 significantly enhances the expression of cardiac-genic genes, including Nkx2.5 and Gata-4, and promotes the differentiation of hUC-MSCs into cardiomyocyte-like cells.

The Role of Cytokines in Interactions of Mesenchymal Stem Cells and Breast Cancer Cells

2020 ◽  
Vol 15 ◽  
Author(s):  
Hariharan Jayaraman ◽  
Nalinkanth V. Ghone ◽  
Ranjith Kumaran R ◽  
Himanshu Dashora
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Microenvironment ◽  
Cancer Cells ◽  
Cell Communication ◽  
Extra Cellular Matrix ◽  
Cytokine Signaling ◽  
Cellular Matrix

: Mesenchymal stem cells because of its high proliferation, differentiation, regenerative capacity, and ease of availability have been a popular choice in cytotherapy. Mesenchymal Stem Cells (MSCs) have a natural tendency to home in a tumor microenvironment and acts against it, owing to the similarity of the latter to an injured tissue environment. Several studies have confirmed the recruitment of MSCs by tumor through various cytokine signaling that brings about phenotypic changes to cancer cells, thereby promoting migration, invasion, and adhesion of cancer cells. The contrasting results on MSCs as a tool for cancer cytotherapy may be due to the complex cell to cell interaction in the tumor microenvironment, which involves various cell types such as cancer cells, immune cells, endothelial cells, and cancer stem cells. Cell to cell communication can be simple or complex and it is transmitted through various cytokines among multiple cell phenotypes, mechano-elasticity of the extra-cellular matrix surrounding the cancer cells, and hypoxic environments. In this article, the role of the extra-cellular matrix proteins and soluble mediators that acts as communicators between mesenchymal stem cells and cancer cells has been reviewed specifically for breast cancer, as it is the leading member of cancer malignancies. The comprehensive information may be beneficial in finding a new combinatorial cytotherapeutic strategy using MSCs by exploiting the cross-talk between mesenchymal stem cells and cancer cells for treating breast cancer.

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