STEM CELLS

Cover image for Vol. 34 Issue 7

Edited By: Jan A. Nolta

Impact Factor: 5.902

ISI Journal Citation Reports © Ranking: 2015: 3/21 (CELL & TISSUE ENGINEERING); 8/70 (Hematology); 14/161 (Biotechnology & Applied Microbiology); 24/213 (Oncology); 34/187 (Cell Biology)

Online ISSN: 1549-4918

Featured

  • In Vivo Interleukin-13-Primed Macrophages Contribute to Reduced Alloantigen-Specific T Cell Activation and Prolong Immunological Survival of Allogeneic Mesenchymal Stem Cell Implants

    In Vivo Interleukin‐13‐Primed Macrophages Contribute to Reduced Alloantigen‐Specific T Cell Activation and Prolong Immunological Survival of Allogeneic Mesenchymal Stem Cell Implants

    Transplantation of IL13-producing MSCs induces an alternatively activated phenotype in graft-infiltrating macrophages (and microglia). Representative immunofluorescence images of FVB MSC-Luc/eGFPb and FVB MSC-Luc/eGFP/IL13 implants in muscle (5 days postgrafting) or brain (7 days postgrafting) of C57BL/6 mice (n = 5/condition). Iba1 and F4/80 were used as general macrophage/microglia markers, MHCII as a typical activation marker, and Arg1, Ym1, and FIZZ1 as markers of alternative M2a activation. In addition, graft sites were evaluated for the presence of CD3+ and CD8+ T cells. Secondary antibodies were coupled to Alexa Fluor 555 for red fluorescence, Alexa Fluor 350 for blue fluorescence or Cy5 for far red fluorescence (for the F4/80 + MHCII double staining, MHCII was stained in far red, but is represented here in blue). Images were acquired using the ×4 (top row) and ×20 (other rows, both main images and insets) objective lenses. Scale bars = 500 µm in the top row and 50 µm in all other images (both main images and insets). Abbreviations: eGFP, enhanced green fluorescent protein; IL, interleukin; MHC, major histocompatibility complex; MSC, mesenchymal stem cell.

  • Foxi3 Deficiency Compromises Hair Follicle Stem Cell Specification and Activation

    Foxi3 Deficiency Compromises Hair Follicle Stem Cell Specification and Activation

    Foxi3 expression colocalizes with stem cell markers only at the beginning of hair morphogenesis and later in telogen follicle secondary hair germs. Co-localization of Foxi3 (red) with stem cell markers Lhx2, Nfatc1, and Sox9 (green) at different stages of hair morphogenesis and at the first telogen was analyzed by double immunostaining. (A): Foxi3 was co-expressed with Lhx2 in hair placodes and in the leading front of the growing hair follicle. At advanced stages of development, Foxi3+ cells in the center were negative for Lhx2. At telogen, Foxi3+ cells in the hair germ also expressed Lhx2. (B): Nfatc1 was undetectable at the placode stage, but co-localized with Foxi3 at the hair peg stage (arrowhead). In advanced hair follicles (E18.5), Foxi3+ cells in the center were negative for Nfatc1, which was expressed in the prebulge region (arrowhead). At telogen, Nfatc1 marked the quiescent SCs of the upper bulge and was not co-expressed with Foxi3 in the hair germ. (C): Some cells of the placode were positive for both Foxi3 and Sox9. At the hair germ stage, Sox9 did not co-localize with Foxi3+ cells at the leading front, but a small number of cells positive for both Foxi3 and Sox9 appeared in the middle of the growing hair peg. In addition, Sox9 was detected in the upper part of the follicle (arrowhead). At telogen, Foxi3+ cells in the hair germ were also positive for Sox9, but the latter was expressed also in the bulge. Scale bar = 50 μm. Abbreviations: E, embryonic day.

  • Intravenous Transplantation of Mesenchymal Progenitors Distribute Solely to the Lungs and Improve Outcomes in Cervical Spinal Cord Injury

    Intravenous Transplantation of Mesenchymal Progenitors Distribute Solely to the Lungs and Improve Outcomes in Cervical Spinal Cord Injury

    Chondroitin sulfate proteoglycan and macrophage profiles in cervical contusion injury control and treatment groups 8 weeks after injury. Gross overview of chondroitin sulfate proteoglycan deposit stained with CS-56 when IV injected with (A) HBSS D1 and (C) MPCs D1. White box outlines the injury site with the corresponding micro view for each group seen in B and D respectively. Gross overview of CD11b+ macrophage response, 8 weeks after injury, when IV injected with (E) HBSS D1 and (G) MPCs D1. White box outlines the injury site with corresponding micro view for each group seen in F and H respectively. (I) shows the % area of CD11b coverage in areas rostral, center and caudal to the injury site (*p < .05, **p < .001). Quantitation data shows a decrease in CD11b+ staining when mice received MPCs at D1 and D3, with the center of the lesion having the most statistically significant difference when compared to controls. Scale bar = 200 μm. Abbreviations: HBSS, Hank's Buffered Saline Solution; MPC, mesenchymal progenitor cells.

  • Silencing of Antichondrogenic MicroRNA-221 in Human Mesenchymal Stem Cells Promotes Cartilage Repair In Vivo

    Silencing of Antichondrogenic MicroRNA‐221 in Human Mesenchymal Stem Cells Promotes Cartilage Repair In Vivo

    Evaluation of the in vitro chondrogenic potential of antagomiR-221 treated human mesenchymal stromal cells (hMSCs) from Wharton's jelly. At day 21 of culture, hMSCs pellets were immunostained for the matrix proteins collagen type II and collagen type X (A) and for the chondroregulatory transcription factors Sox9, TRPS1 and Slug (B). Representative optical photomicrographs are reported. Scale bars = 100 µm and insert bar in (B) = 200 µm. Protein levels were quantified by densitometric analysis of immunohistochemical pictures using ImageJ software and expressed as % of positive area of the pellet (three replicates per three donor). Data are presented as median and interquartile range. Statistical analysis was performed versus untreated cells (§) and antagomiR-Scr (*) or TGF-β (^) treated hMSCs (p ≤ .05). Abbreviation: TFG-β, transforming growth factor beta.

  • Different Concentrations of FGF Ligands, FGF2 or FGF8 Determine Distinct States of WNT-Induced Presomitic Mesoderm

    Different Concentrations of FGF Ligands, FGF2 or FGF8 Determine Distinct States of WNT‐Induced Presomitic Mesoderm

    The FGF ligand concentration has an impact on the presomitic mesoderm (PSM) state. (A): Heat map depicting the differential regulation of genes between the indicated samples. CH-mediated PSM induction with high or low FGF concentration led to induction of posterior PSM or somatic/anterior PSM genes, respectively. (B): Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) validations of the differentially expressed genes between the indicated samples. Error bars: mean ± SD (n = 3). *, p < .05 (Student's t test). (Hes7: 50 ng/ml of FGF8 was used for FGF8 High/CH treatment). Influence of FGF concentration on PSM genes. (C): Expression analysis of marker genes in the indicated samples by qRT-PCR. Error bars: mean ± SD (n = 3). Combination of FGF2 and FGF8 during CH-driven PSM induction affected expression of Tbx6 and Msgn1. Abbreviations: CH, CHIR99021; ESC, embryonic stem cells; FGF, fibroblast growth factor.

  • Lineage-Specific Early Differentiation of Human Embryonic Stem Cells Requires a G2 Cell Cycle Pause

    Lineage‐Specific Early Differentiation of Human Embryonic Stem Cells Requires a G2 Cell Cycle Pause

    Transcriptome analysis of early differentiation into mesendoderm. (A): Representative immunofluorescence staining of BRACHYURY (red) and SOX17 (green) over a mesendodermal differentiation time course. Green arrows point to cells staining positive for SOX17, as expression is very low. Nuclei are stained with DAPI (blue) (scale bars: 20 µm). (B): Principal Component Analysis (PCA) of the time points and replicates for mesendodermal differentiation of human embryonic stem cells (hESCs) from global expression profiling of four time points (Undifferentiated (0 hour), 8 hours (8 hours), 1 day (24 hours), and 3 days (72 hours) (n = 3) by microarray analysis. (C): Venn diagram of the number of gene with expression changes greater than 1.5-fold, and p value and FDR p values < .05, at each time point compared to undifferentiated hESCs. The total number of genes changed at each time point is in brackets.

  • Inhibition of Focal Adhesion Kinase Signaling by Integrin α6β1 Supports Human Pluripotent Stem Cell Self-Renewal

    Inhibition of Focal Adhesion Kinase Signaling by Integrin α6β1 Supports Human Pluripotent Stem Cell Self‐Renewal

    Activation of integrin β1 signaling induces focal adhesions and reduction in Oct4 expression in human embryonic stem cells (hESC). Representative micrographs of a hESC colony (top panel) immunostained with specific antibodies for NT FAK to identified focal adhesion sites (white arrows). Oct4 specific antibody was used to verify the undifferentiated state of hESCs (yellow arrows). Cells were counterstained with DAPI. Treatment with integrin β1 activating antibodies to undifferentiated hESCs (bottom panel) induces the formation of focal adhesion sites. Note this treatment also induced a reduction in nuclear expression of Oct4. Scale bar = 100 μm. Representative micrographs in inserts at the lower left corner of top panel show control immunostaining, in which first antibody was omitted. Abbreviations: DAPI, 4′, 6-diamidino-2-phenylindole; FAK, focal adhesion kinase; NT, N terminal domain.

  • In Vivo Interleukin‐13‐Primed Macrophages Contribute to Reduced Alloantigen‐Specific T Cell Activation and Prolong Immunological Survival of Allogeneic Mesenchymal Stem Cell Implants
  • Foxi3 Deficiency Compromises Hair Follicle Stem Cell Specification and Activation
  • Intravenous Transplantation of Mesenchymal Progenitors Distribute Solely to the Lungs and Improve Outcomes in Cervical Spinal Cord Injury
  • Silencing of Antichondrogenic MicroRNA‐221 in Human Mesenchymal Stem Cells Promotes Cartilage Repair In Vivo
  • Different Concentrations of FGF Ligands, FGF2 or FGF8 Determine Distinct States of WNT‐Induced Presomitic Mesoderm
  • Lineage‐Specific Early Differentiation of Human Embryonic Stem Cells Requires a G2 Cell Cycle Pause
  • Inhibition of Focal Adhesion Kinase Signaling by Integrin α6β1 Supports Human Pluripotent Stem Cell Self‐Renewal

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STEM CELLS Video Highlight

Video abstract from Drs. Serena, Keiran, Ceperuelo-Mallafre, Ejarque, Fradera, Roche, Nuñez-Roa, Vendrell, and Férnandez-Veledo on their recently published STEM CELLS paper entitled, "Obesity and Type 2 Diabetes Alters the Immune Properties of Human Adipose Derived Stem Cells" Read the Paper here

Video abstract from Dr. Allen on his recently published STEM CELLS paper entitled, "Angiopellosis as an Alternative Mechanism of Cell Extravasation" Read the Paper here

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