STEM CELLS

Cover image for Vol. 34 Issue 5

Edited By: Jan A. Nolta

Impact Factor: 6.523

ISI Journal Citation Reports © Ranking: 2014: 2/21 (CELL & TISSUE ENGINEERING); 4/68 (Hematology); 10/163 (Biotechnology & Applied Microbiology); 20/211 (Oncology); 33/184 (Cell Biology)

Online ISSN: 1549-4918

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  • Fascia Origin of Adipose Cells

    Fascia Origin of Adipose Cells

    Formation of adipose lobule in fascia. Superficial fasciae from 7-week-old rats were whole-mounted. Adipose lobules newly formed in fascia were stained by Nile Red (A, B) and Oil Red (C, D). Nuclei were stained with Hoechst 33258. Some adipocytes (ad) appeared to overlay on top of other adipocytes (B, D, boxes), indicating the formation of three-dimensional adipose tissue (A–D). H&E stain (E–G) and Victoria blue-Ponceau S stain (H, I) showed that adipose lobules originated from the adventitia of the main blood vessel (E, H) and extended along abundant inferior branches. At the front of adipose lobules, capillary vessels wrapped and passed ahead of mature adipocytes to form a distal neovasculature niche (F, G, I). Red blood cells (RBC) were clearly seen within blood capillaries around mature adipocytes in fasciae of rats killed without draining the blood from the body (F, G). Histological relationships of microvessels (bv), elastic fibers (f, blue threads), mast cells (blue cells), and adipocytes (ad) in fascia were shown (E–I). In the final box (J), we propose a schematic model of the fascia origin of adipose cells, explaining both adipose neogenesis and expansion (J). Adipose precursor cells reside in the vasculature of fascia and are physiologically active. During postnatal growth, adipose cells gradually arise from fascial preadipocytes to form primitive adipose lobules. At the lobule front, capillaries wrap around and pass ahead of adipocytes to form the distal neovasculature, which might replenish the pool of preadipocytes and supply nutrients and hormones to ensure continuous adipogenesis in situ (J). When some adipocytes overlay on top of other adipocytes, a primitive 3D adipose tissue is formed in the fascia. Thereafter this fascia naturally becomes the connective tissue continuum of renascent adipose tissue, and still preserves fascial preadipocytes and niche to ensure regeneration of adipocytes inside adipose tissue (J). With continuous adipogenesis, primitive adipose lobules in superficial fascia, a subcutaneous nonadipose tissue, may gradually expand to from a rudiment of subcutaneous adipose tissue (J).

  • Peribiliary Glands as a Niche of Extrapancreatic Precursors Yielding Insulin-Producing Cells in Experimental and Human Diabetes

    Peribiliary Glands as a Niche of Extrapancreatic Precursors Yielding Insulin‐Producing Cells in Experimental and Human Diabetes

    Peribiliary glands (PBGs) in induced experimental diabetes. (A): Hematoxylin and eosin (H&E) staining of extrahepatic biliary tree (EHBT) in control and STZ-treated samples. At the level of the EHBT, STZ-treated mice showed a significant expansion of the PBG area after high-dose STZ treatment and after 30 days (D30) and 90 days (D90) of low-dose STZ treatment in comparison with controls. Original magnification: × 20. (B): H&E staining of hepatopancreatic ampulla in control and STZ-treated samples. At the level of the hepatopancreatic ampulla, STZ-treated mice showed a significant expansion of PBG area after high-dose STZ treatment, and after 30 and 90 days of low-dose STZ treatment in comparison with controls. Original magnification: × 20. (C): PAS staining of EHBT in control and STZ-treated samples. STZ treatment resulted in an increase of PAS-positive cells within PBGs. Original magnification: × 20. Abbreviations: CTR, control; PAS, Periodic Acid Schiff; STZ, streptozotocin.

  • Wnt3a, a Protein Secreted by Mesenchymal Stem Cells Is Neuroprotective and Promotes Neurocognitive Recovery Following Traumatic Brain Injury

    Wnt3a, a Protein Secreted by Mesenchymal Stem Cells Is Neuroprotective and Promotes Neurocognitive Recovery Following Traumatic Brain Injury

    Intravenous (IV)-MSC treatment protects neural stem cells from TBI-induced loss and enhances neurogenesis in the ipsilateral dentate gyrus. Confocal images on coronal sections of mouse dorsal dentate gyrus were stained for DCX (red), BrdU (green), and counterstained with Hoechst for nuclei (blue). (A): Ipsilateral dentate gyrus images reveal loss of DCX+ve neural stem cells 3-days post-TBI and rescue by IV-MSC treatment. By day 7 DCX+ve neural stem cells in the ipsilateral dentate gyrus recover to similar levels for both TBI alone and IV-MSC-treated mice. Scale bar = 100 μm. (B): Higher magnification view of the dentate gyrus 3 days post-TBI shows preservation of neurons by IV-MSCs in SGZ and an increase in the GCL as indicated by the arrows. Scale bar = 50 μm. (C, D): Quantification of ipsilateral dentate gyrus (C) DCX + and (D) DCX+BrdU + cells. ***, p < .001; **, p < .01; *, p < .05, data are means ± SEM, n = 4 mice, four sections per mouse. Abbreviations: BrdU, bromodeoxyuridine; DCX, doublecortin; DAPI, 4′,6-diamidino-2-phenylindole; GCL, granular cell layer; MSC, mesenchymal stem cell; SGZ, subgranular zone; TBI, traumatic brain injury.

  • Hyaluronan Is Crucial for Stem Cell Differentiation into Smooth Muscle Lineage

    Hyaluronan Is Crucial for Stem Cell Differentiation into Smooth Muscle Lineage

    HA niche promotes esSMCs neointimal accumulation and neovascularization. (A): Embryonic stem cells (5 × 105) were seeded in the outer layer of a decellularized mouse thoracic aorta in a bioreactor system, either in the presence (HA) or absence (Control) of HMW-HA in the circulating medium followed by application of shear stress. After 1 week, the vessels were harvested and embedded in mouse liver for nitrogen freezing. The frozen sections were subjected to immunofluorescence staining for the smooth muscle cell (SMC) markers α-SMA, and calponin. Graph (B) represents mean ± SEM from three independent experiment. (C) esSMCs (5 × 105) maintained in normal differentiation medium (control) or HMW-HA (HA) were mixed with esECs (5 × 105) then added to a Matrigel plug before subcutaneous injection into a LacZ mouse. After 1 week the Matrigel plug was removed and sections were stained for EC marker CD31 or SMC marker sm22-α (green). esSMCs were labeled with Vybrant (red) before implantation in order to be distinguished from esECs. In control samples esECs stained positive for CD31 but exhibited weak interaction with the vybrant stained esSMCs. In HA treated samples vybrant stained esSMCs displayed enhanced sm22-α co-localization (yellow) and interacted with esECs to form substantially denser and more robust tube-like structures (indicated by arrows). (D): The number of tubes that were either calponin or CD31 positive were quantified in five random fields of view at x10 magnification, mean ± SEM n = 6 animals. (E): Vena cava segments were surgically removed from C57BL/6 mice under anesthesia and subsequently grafted into carotid arteries of apoE-deficient recipient mice. esSMCs (5 × 105) were stained with a Vybrant cell tracker dye before being seeded onto the adventitial side to envelop the vein grafts. Grafted tissue fragments were harvested 2 weeks after surgery and stained with H&E and immunofluorescence stained with SMMHC and DAPI. Vein segments were seeded with esSMCs that were differentiated in differentiation medium in the absence of (control) or presence of HMW-HA (HA). White squares represent the neointima, and the areas of neointimal leisions in vein grafts were quantified as described in methods section. Graph (F) represents mean ± SEM, six animals per group. Bars, 100 μm. All analyses based on Student's t test. *, p < .05; **, p < .01, versus control. Abbreviations: HA, hyaluronan; H&E hematoxylin and eosin.

  • Peroxiredoxin II Is Essential for Maintaining Stemness by Redox Regulation in Liver Cancer Cells

    Peroxiredoxin II Is Essential for Maintaining Stemness by Redox Regulation in Liver Cancer Cells

    Association of Prx II with cancer stem cell in HCC cells. (A): Representative image of EpCAM(+)/K19(+) HCC showing Prx II expression in contrast to EpCAM(−)/K19(−) HCC without expression of Prx II (magnification, × 200). (B): Comparison of proportions of Prx II expressing in EpCAM(+)/K19(+) HCCs and EpCAM(−)/K19(−) HCCs. (C): Expression levels of Sox2 in Huh7 cells transfected with siPrx II. (D): Proportions of 2′,7′-dichlorodihydrofluorescein diacetate, annexin V, EpCAM, and CD133 positive in Huh7 cells transfected with siPrx II by flow cytometric analysis. The data are the mean ± SEM (n = 5 per group), *p < .05. Abbreviations: EpCAM, epithelial-cell adhesion molecules; HCC, hepatocellular carcinoma; Prx II, peroxiredoxin II; K19, cytokeratin 19.

  • Stem Cells Antigen-1 Enriches for a Cancer Stem Cell-Like Subpopulation in Mouse Gastric Cancer

    Stem Cells Antigen‐1 Enriches for a Cancer Stem Cell‐Like Subpopulation in Mouse Gastric Cancer

    Clinical significance of Sca-1 in human gastric cancer. Clinical significance of Sca-1 in human gastric cancer. (A): A hierarchical clustering dendrogram for pretreatment biopsy samples of chemotherapy-treated gastric cancer patients, which was generated using genes overexpressed in Sca-1high S1 cells (Sca-1 signature). Red and green denotes high and low gene expression levels, respectively. (B): Kaplan-Meier plots for overall survival of 2 clusters generated by (A). Patients who overexpressed genes in the Sca-1 signature had significantly shorter overall survival (Log-rank, p = .005). Red and black lines denote Kaplan-Meir plots for clusters with high- and low-expression of genes in the Sca-1 signature, respectively.

  • A Synthetic Polymer Scaffold Reveals the Self-Maintenance Strategies of Rat Glioma Stem Cells by Organization of the Advantageous Niche

    A Synthetic Polymer Scaffold Reveals the Self‐Maintenance Strategies of Rat Glioma Stem Cells by Organization of the Advantageous Niche

    Schematic summaries of the synthetic polymer-based approach to GSCs and GSC niche. (A): Self-protecting strategies of GSCs revealed by the PU10 polymer. Left panel; A urethane polymer PU10 constructs artificial microenvironments on the dish surface by capturing cell- or serum-derived factors, and mimics the physiological features of the GSC niche, on which GSCs can selectively proliferate and exhibit high tumorigenicity. Middle panel; PU10-identified niche elements are found to be supplied from nontumorigenic but tumor-supporting GSC progenies in conventional cultures, indicating the presence of a self-protecting strategy taken by GSCs through adaptive differentiation. Right panel; such a survival strategy of GSCs are validated in vivo. Perivascular and immune niche supply PU10-identified niche elements. GSCs have the great capacities to reconstruct their own niche by exploiting host Mφs to develop into protumoral ones, as well as transdifferentiation into VECs (right panel). (B): Conceptual refinement of the CSC niche therapy. Disrupting CSC niche theoretically appears to impair the self-renewal of CSCs and thereby inhibit the progression and recurrence of tumors. However, considering our present findings that CSCs can accommodate themselves at a site where the CSC niche is missing or disrupted, by self-organizing their niche, it is indispensable not merely to tackle the CSC niche itself but also to elucidate how CSCs sense their disadvantageous situation. This will hopefully open a new therapeutic window for CSC eradication. Blue color denotes the activating CSCs that can reconstruct the niche. Abbreviations: CSC, cancer stem cell; GSC, glioma CSC; VEC, vascular endothelial cells.

  • Fascia Origin of Adipose Cells
  • Peribiliary Glands as a Niche of Extrapancreatic Precursors Yielding Insulin‐Producing Cells in Experimental and Human Diabetes
  • Wnt3a, a Protein Secreted by Mesenchymal Stem Cells Is Neuroprotective and Promotes Neurocognitive Recovery Following Traumatic Brain Injury
  • Hyaluronan Is Crucial for Stem Cell Differentiation into Smooth Muscle Lineage
  • Peroxiredoxin II Is Essential for Maintaining Stemness by Redox Regulation in Liver Cancer Cells
  • Stem Cells Antigen‐1 Enriches for a Cancer Stem Cell‐Like Subpopulation in Mouse Gastric Cancer
  • A Synthetic Polymer Scaffold Reveals the Self‐Maintenance Strategies of Rat Glioma Stem Cells by Organization of the Advantageous Niche

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STEM CELLS Video Highlight

Video abstract from Drs. Sakayori, Kikkawa, Tokuda, Kiryu, Yoshizaki, Kawashima, Yamada, Arai, Kang, Katagiri, Shibata, Innis, Arita, and Osumi on their STEM CELLS paper entitled, "Maternal dietary imbalance between omega-6 and omega-3 polyunsaturated fatty acids impairs neocortical development via epoxy metabolites" Read the Paper here

Video abstract from Drs. Evans and Janeczek on their recently published STEM CELLS paper entitled, "Transient Canonical Wnt Stimulation Enriches Human Bone Marrow Mononuclear Cell Isolates for Osteoprogenitors" Read the Paper here

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