Three-Dimensional Human Neural Stem Cell Models to Mimic Heparan Sulfate Proteoglycans and the Neural Niche

2021 ◽  
Vol 47 (03) ◽  
pp. 308-315
Author(s):  
Ian W. Peall ◽  
Rachel K. Okolicsanyi ◽  
Lyn R. Griffiths ◽  
Larisa M. Haupt
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Three Dimensional ◽  
3D Models ◽  
Side Chain ◽  
Cell Models ◽  
Sulfation Pattern ◽  
Cell Niche ◽  
Stem Cell Models

AbstractHeparan sulfate proteoglycans (HSPGs) are a diverse family of polysaccharides, consisting of a core protein with glycosaminoglycan (GAG) side chains attached. The heterogeneous GAG side-chain carbohydrates consist of repeating disaccharides, with each side chain possessing a specific sulfation pattern. It is the variable sulfation pattern that allows HSPGs to interact with numerous ligands including growth factors, cytokines, chemokines, morphogens, extracellular matrix (ECM) glycoproteins, collagens, enzymes, and lipases. HSPGs are classified according to their localization within an individual cell, and include the membrane bound syndecans (SDCs) and glypicans (GPCs), with perlecan, agrin, and type-XVIII collagen secreted into the ECM. The stem cell niche is defined as the environment that circumscribes stem cells when they are in their naïve state, and includes the ECM, which provides a complex contribution to various biological processes during development and throughout life. These contributions include facilitating cell adhesion, proliferation, migration, differentiation, specification, and cell survival. In contrast, HSPGs play an anticoagulant role in thrombosis through being present on the luminal surface of cells, while also playing roles in the stimulation and inhibition of angiogenesis, highlighting their varied and systemic roles in cellular control. To fully understand the complexities of cell-cell and cell–matrix interactions, three-dimensional (3D) models such as hydrogels offer researchers exciting opportunities, such as controllable 3D in vitro environments, that more readily mimic the in vivo/in situ microenvironment. This review examines our current knowledge of HSPGs in the stem cell niche, human stem cell models, and their role in the development of 3D models that mimic the in vivo neural ECM.

MESENCHYMAL TNFR1 EXPRESSION PRESERVES THE COLONIC EPITHELIAL STEM CELL NICHE

2021 ◽  
Vol 27 (Supplement_1) ◽  
pp. S7-S8
Author(s):  
Safina Gadeock ◽  
Cambrian Liu ◽  
Brent Polk
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Mesenchymal Cells ◽  
Epithelial Stem Cells ◽  
Epithelial Stem Cell ◽  
Long Term Treatment ◽  
Lgr5 Expression ◽  
Cell Niche

Abstract Tumor necrosis factor (TNF) is a highly expressed cytokine in inflammatory bowel disease (IBD). Although TNF can induce colonic epithelial dysfunction and apoptosis, recent studies suggest that TNF signalling promotes epithelial wound repair and stem cell function. Here we investigated the role of TNF receptor 1 (TNFR1) in mediating TNF’s effects on colonic epithelial stem cells, integral to mucosal healing in colitis. We demonstrate that Tnfr1-/- mice exhibit loss in Lgr5 expression (-52%, p<0.02; N=6) compared to wildtype (WT) controls. However, the opposite result was found in vitro, wherein murine Tnfr1-/- colonoids demonstrated a significant increase in Lgr5 expression (66%, p<0.007; N=6) compared to WT colonoids. Similarly, human colonoids treated with an anti-TNFR1 antibody also demonstrated an increase in Lgr5 expression, relative to IgG controls. To resolve the contradiction in the in vivo versus in vitro environment, we hypothesized that mesenchymal TNFR1 expression regulates the epithelial stem cell niche. To determine the relationships between these cell types, we co-cultured WT or Tnfr1-/- colonoids with WT or Tnfr1-/- colonic myofibroblasts (CMFs). We found that epithelial Lgr5 expression was significantly higher (by 52%, p<0.05; N=3) when co-cultured with WT compared to TNFR1-/- myofibroblasts. The loss of TNFR1 expression in vivo increases the number of αSMA+ mesenchymal cells by nearly 56% (N=6) but considerably reduces the pericryptal PDGFRα+ cells, suggesting modifications in mesenchymal populations that contribute to the epithelial stem cell niche. Functionally, primary Tnfr1-/--CMFs displayed PI3k (p<0.001; N=3) and MAPK (p<0.01; N=3)-dependent increases in migration, proliferation, and differentiation, but RNA profiling demonstrated by diminished levels of stem cell niche factors, Rspo3 (-80%, p<0.0001; N=6) and Wnt2b (-63%, p<0.008; N=6) compared to WT-CMFs. Supplementation with 50ng recombinant Rspo3 for 5 d to Lgr5-GFP organoids co-cultured with TNFR1-/--CMFs restored Lgr5 expression to wildtype levels. Therefore, TNFR1-mediated TNF signalling in mesenchymal cells promotes their ability to support an epithelial stem cell niche. These results should motivate future studies of the stem cell niche in the context of long-term treatment with anti-TNF therapies.

scholarly journals Lymphatic vessels interact dynamically with the hair follicle stem cell niche during skin regeneration in vivo

2019 ◽  
Vol 38 (19) ◽  
Author(s):  
Daniel Peña‐Jimenez ◽  
Silvia Fontenete ◽  
Diego Megias ◽  
Coral Fustero‐Torre ◽  
Osvaldo Graña‐Castro ◽  
...  
Keyword(s):  
Stem Cell ◽  
Hair Follicle ◽  
Stem Cell Niche ◽  
Lymphatic Vessels ◽  
Skin Regeneration ◽  
Hair Follicle Stem Cell ◽  
Cell Niche

scholarly journals Three-dimensional induced pluripotent stem-cell models of human brain angiogenesis

2020 ◽  
Vol 132 ◽  
pp. 104042 ◽  
Author(s):  
Raleigh M. Linville ◽  
Diego Arevalo ◽  
Joanna C. Maressa ◽  
Nan Zhao ◽  
Peter C. Searson
Keyword(s):  
Stem Cell ◽  
Human Brain ◽  
Pluripotent Stem Cell ◽  
Three Dimensional ◽  
Induced Pluripotent Stem Cell ◽  
Cell Models ◽  
Induced Pluripotent ◽  
Stem Cell Models ◽  
Brain Angiogenesis

scholarly journals The bone metastasis niche in breast cancer: potential overlap with the haematopoietic stem cell niche in vivo

2019 ◽  
Vol 17 ◽  
pp. 100244 ◽  
Author(s):  
Gloria Allocca ◽  
Russell Hughes ◽  
Ning Wang ◽  
Hannah K Brown ◽  
Penelope D Ottewell ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Stem Cell ◽  
Bone Metastasis ◽  
Stem Cell Niche ◽  
Haematopoietic Stem Cell ◽  
Cell Niche

scholarly journals Three-dimensional structure of the mammalian limbal stem cell niche

2015 ◽  
Vol 93 ◽  
pp. n/a-n/a
Author(s):  
V. Borderie ◽  
K. Grieve ◽  
D. Ghoubay ◽  
C. Georgeon ◽  
O. Thouvenin ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Niche ◽  
Three Dimensional ◽  
Dimensional Structure ◽  
Three Dimensional Structure ◽  
Limbal Stem Cell ◽  
Cell Niche ◽  
Limbal Stem Cell Niche

Ectopic Human Mesenchymal Stem Cell-Coated Scaffolds Create An In Vivo Leukemia Niche in NOD/SCID Mice.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 559-559
Author(s):  
Sarah Rivkah Vaiselbuh ◽  
Morris Edelman ◽  
Jeffrey Michael Lipton ◽  
Johnson M. Liu
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Stem Cell ◽  
Stem Cell Niche ◽  
Scid Mice ◽  
Cxcr4 Antagonist ◽  
Cell Niche

Abstract Abstract 559 Introduction: Different cellular components of the normal hematopoietic niche have been identified. However, the niche for malignant hematopoiesis remains to be elucidated. Recent work of other groups has suggested that hematopoietic stem cells (HSC) within the bone marrow anchor themselves in place by attaching to osteoblasts and/or vascular sinusoid endothelial cells. We have recently identified mesenchymal stem cells (MSC) as niche-maker cells and found a crucial role of the SDF-1/CXCR4 axis in this process. Stromal Derived Factor-1 (SDF-1/CXCL12) regulates stem cell trafficking and the cell cycle via its receptor CXCR4. Methods: Polyurethane scaffolds, coated in vitro with human bone marrow MSC, were implanted subcutaneously in non-irradiated NOD/SCID mice. CD34+ HSC or primary AML cells (from a leukapheresis product) were injected either in situ or retro-orbitally in the mice and analyzed for engraftment. The mice were treated twice per week with in situ injections of SDF-1, AMD3100 (a CXCR4 antagonist) or PBS (control). After 2 to 4 weeks, the scaffolds were processed and evaluated for cell survival in the mesenchymal niche by immunohistochemistry. Results: We created in vitro MSC-coated scaffolds that retained inoculated AML cells in the presence of SDF-1, while AML cells seeded on empty scaffolds were not retained. In vivo in NOD/SCID mice, the MSC-coated scaffolds, in the presence of SDF-1 enabled homing of both in situ injected normal CD34+ HSC and retroorbital- or in situ injected primary human AML cells. The scaffolds were vascularized and showed osteoclasts and adipocytes present, suggestive of an ectopic human bone marrow microenvironment in the murine host. Finally, the SDF-1-treated scaffolds showed proliferation of the MSC stromal layer with multiple adherent AML cells, while in the AMD3100-treated scaffolds the stromal lining was thin and disrupted at several points, leaving AML cells free floating in proximity. The PBS-treated control-scaffold showed a thin single cell MSC stromal layer without disruption, with few AML cells attached. Conclusion: The preliminary data of this functional ectopic human microenvironment in NOD/SCID mice suggest that AMD3100 (a CXCR4 antagonist) can disrupt the stem cell niche by modulation of the mesenchymal stromal. Further studies are needed to define the role of mesenchymal stem cells in maintaining the hematopoietic/leukemic stem cell niche in vivo. In Vivo Leukemia Stem Cell Niche: (A) Empty polyurethane scaffold. (B)Vascularization in SQ implanted MSC-coated scaffold (s) niche in NOD/SCID mice. (C) DAB Peroxidase (brown) human CD45 positive nests of AML cells (arrows) 1 week after direct in situ AML injection. (D) Human CD45 positive myeloid cells adhere to MSC in vivo (arrows). Disclosures: No relevant conflicts of interest to declare.

scholarly journals The Drosophila ZO-1 protein Polychaetoid suppresses Deltex-regulated Notch activity to modulate germline stem cell niche formation

Open Biology ◽  
2017 ◽  
Vol 7 (4) ◽  
pp. 160322 ◽  
Author(s):  
Hideyuki Shimizu ◽  
Marian B. Wilkin ◽  
Simon A. Woodcock ◽  
Alessandro Bonfini ◽  
Yvonne Hung ◽  
...  
Keyword(s):  
Stem Cell ◽  
Cell Surface ◽  
Stem Cell Niche ◽  
Activation Mechanism ◽  
Germline Stem Cell ◽  
Ligand Interaction ◽  
Alternative Means ◽  
Cell Niche ◽  
Notch Activation

The developmental signalling protein Notch can be proteolytically activated following ligand-interaction at the cell surface, or can be activated independently of its ligands, following Deltex (Dx)-induced Notch endocytosis and trafficking to the lysosomal membrane. The means by which different pools of Notch are directed towards these alternative outcomes remains poorly understood. We found that the Drosophila ZO-1 protein Polychaetoid (Pyd) suppresses specifically the Dx-induced form of Notch activation both in vivo and in cell culture assays. In vivo we confirmed the physiological relevance and direction of the Pyd/Dx interaction by showing that the expanded ovary stem cell niche phenotypes of pyd mutants require the presence of functional Dx and other components that are specific to the Dx-induced Notch activation mechanism. In S2 cells we found that Pyd can form a complex with Dx and Notch at the cell surface and reduce Dx-induced Notch endocytosis. Similar to other known activities of ZO-1 family proteins, the action of Pyd on Dx-induced endocytosis and signalling was found to be cell density dependent. Thus, together, our results suggest an alternative means by which external cues can tune Notch signalling through Pyd regulation of Dx-induced Notch trafficking.

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