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  1. Article ; Online: Examining Mechanisms for Voltage-Sensitive Calcium Channel-Mediated Secretion Events in Bone Cells.

    Reyes Fernandez, Perla C / Wright, Christian S / Farach-Carson, Mary C / Thompson, William R

    Calcified tissue international

    2023  Volume 113, Issue 1, Page(s) 126–142

    Abstract: In addition to their well-described functions in cell excitability, voltage-sensitive calcium channels (VSCCs) serve a critical role in calcium ( ... ...

    Abstract In addition to their well-described functions in cell excitability, voltage-sensitive calcium channels (VSCCs) serve a critical role in calcium (Ca
    MeSH term(s) Calcium/metabolism ; Signal Transduction ; Calcium Channels/metabolism ; Osteocytes/metabolism ; Biological Transport
    Chemical Substances Calcium (SY7Q814VUP) ; Calcium Channels
    Language English
    Publishing date 2023-06-01
    Publishing country United States
    Document type Journal Article ; Review ; Research Support, N.I.H., Extramural
    ZDB-ID 304266-2
    ISSN 1432-0827 ; 0944-0747 ; 0008-0594 ; 0171-967X
    ISSN (online) 1432-0827
    ISSN 0944-0747 ; 0008-0594 ; 0171-967X
    DOI 10.1007/s00223-023-01097-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Human Minor Salivary Glands: A Readily Available Source of Salivary Stem/Progenitor Cells for Regenerative Applications.

    Barrows, Caitlynn M L / Wu, Danielle / Young, Simon / Farach-Carson, Mary C

    Methods in molecular biology (Clifton, N.J.)

    2023  Volume 2749, Page(s) 25–38

    Abstract: Resident stem/progenitor cells within the secretory salivary glands offer a potential therapeutic resource for use in the regeneration of salivary glands needed to restore saliva production in patients with chronic xerostomia, or dry mouth. Methods were ... ...

    Abstract Resident stem/progenitor cells within the secretory salivary glands offer a potential therapeutic resource for use in the regeneration of salivary glands needed to restore saliva production in patients with chronic xerostomia, or dry mouth. Methods were developed previously to isolate human stem/progenitor cells (hS/PCs) from major salivary glands (parotid/submandibular). Abundant minor salivary glands located in readily accessible locations in the oral cavity and lip could provide an additional valuable therapeutic resource. An advantage of this cell resource is that these minor glands about the size of grape seeds can be harvested from healthy donors using minimally invasive surgical procedures. The disadvantage of using minor glands is that they contain many fewer cells than do major glands, and thus harvested cells need to be expanded in the lab to create a therapeutic resource. While earlier work has described isolation of proliferative cell populations from minor salivary glands that could be used in regenerative medicine, most of these expanded cells possess properties of mesenchymal cells rather than the epithelial population that secretes salivary products.Here, we describe in detail our recently established methods to isolate and expand hS/PCs isolated from human labial minor salivary glands. Expanded hS/PC populations are epithelial assessed by their expression of epithelial progenitor markers K5 and K14. Like expandable cell populations previously isolated from the major salivary glands, these cells also express nuclear p63, consistent with their ability to be expanded after explant culture. When hS/PCs with these properties are encapsulated into a customized 3D biomimetic hyaluronic acid-based hydrogel, they will assemble into microstructures that retain some progenitor markers while also beginning to differentiate. The increased expression of secreted mucin MUC-7 was used to demonstrate differentiation and secretory potential in assembled hS/PC microstructures. Compared to hS/PCs from major glands, those from minor salivary glands tend to be more heterogeneous in early passage; thus, use of K5/K14/p63 as an early quality assessment tool is highly recommended. Additionally, hS/PCs from minor glands are sensitive to stress and if mishandled will demonstrate a stress response that leads to their transitioning to a flat, squamous cell-like appearance that is of limited utility in regenerative medicine applications. We conclude that properly handled hS/PCs from minor salivary glands represent a powerful new source of therapeutic cells for applications including treating patients with chronic xerostomia.
    MeSH term(s) Humans ; Salivary Glands, Minor ; Salivary Glands ; Saliva ; Xerostomia/therapy ; Stem Cells
    Language English
    Publishing date 2023-12-21
    Publishing country United States
    Document type Journal Article
    ISSN 1940-6029
    ISSN (online) 1940-6029
    DOI 10.1007/978-1-0716-3609-1_3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Microfluidic coaxial 3D bioprinting of cell-laden microfibers and microtubes for salivary gland tissue engineering.

    Yin, Yu / Vázquez-Rosado, Ephraim J / Wu, Danielle / Viswananthan, Vignesh / Farach, Andrew / Farach-Carson, Mary C / Harrington, Daniel A

    Biomaterials advances

    2023  Volume 154, Page(s) 213588

    Abstract: Replacement therapy for the salivary gland (SG) remains an unmet clinical need. Xerostomia ("dry mouth") due to hyposalivation can result from injury or disease to the SG, such as salivary acinar death caused by radiation therapy (RT) for head and neck ... ...

    Abstract Replacement therapy for the salivary gland (SG) remains an unmet clinical need. Xerostomia ("dry mouth") due to hyposalivation can result from injury or disease to the SG, such as salivary acinar death caused by radiation therapy (RT) for head and neck squamous cell carcinoma (HNSCC). Currently, only palliative treatments exist for xerostomia, and many patients endure deteriorated oral health and poor quality of life. Tissue engineering could offer a permanent solution for SG replacement by isolating healthy SG tissues prior to RT, expanding its cells in vitro, and recreating a functional salivary neogland for implantation post-RT. 3D bioprinting methods potentiate spatial cell deposition into defined hydrogel-based architectures, mimicking the thin epithelia developed during the complex branching morphogenesis of SG. By leveraging a microfluidics-based bioprinter with coaxial polymer and crosslinker streams, we fabricated thin, biocompatible, and reproducible hydrogel features that recapitulate the thin epithelia characteristics of SG. This flexible platform enabled two modes of printing: we produced solid hydrogel fibers, with diameters <100 μm, that could be rastered to create larger mm-scale structures. By a second method, we generated hollow tubes with wall thicknesses ranging 45-80 μm, total tube diameters spanning 0.6-2.2 mm, and confirmed tube patency. In both cases, SG cells could be printed within the thin hydrogel features, with preserved phenotype and high viability, even at high density (5.0 × 10
    MeSH term(s) Humans ; Tissue Engineering ; Microfluidics ; Bioprinting ; Quality of Life ; Hydrogels ; Salivary Glands ; Xerostomia/therapy
    Chemical Substances Hydrogels
    Language English
    Publishing date 2023-08-14
    Publishing country Netherlands
    Document type Journal Article
    ISSN 2772-9508
    ISSN (online) 2772-9508
    DOI 10.1016/j.bioadv.2023.213588
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Book ; Online: Bone and Osteoarthritis

    Bronner, Felix / Farach-Carson, Mary C.

    2008  

    Author's details edited by Felix Bronner, Mary C. Farach-Carson
    Keywords Geriatrics ; Human physiology ; Internal medicine ; Orthopedics ; Pediatrics ; Rheumatology
    Language English
    Publisher Springer-Verlag London Limited
    Publishing place London
    Document type Book ; Online
    HBZ-ID TT050387249
    ISBN 978-1-8462-8513-4 ; 978-1-8462-8701-5 ; 1-8462-8513-5 ; 1-8462-8701-4
    DOI 10.1007/978-1-84628-701-5
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  5. Book: Bone formation

    Bronner, Felix / Farach-Carson, Mary C.

    (Topics in bone biology ; 1)

    2004  

    Author's details Felix Bronner and Mary C. Farach-Carson
    Series title Topics in bone biology ; 1
    Collection
    Keywords Bone Development ; Bone Remodeling ; Knochenbildung ; Störung
    Subject Perturbation ; Beeinträchtigung ; Störungen ; Ossifikation ; Osteogenese ; Verknöcherung ; Knochenneubildung ; Knochenaufbau
    Language English
    Size XV, 160 S. : Ill.
    Publisher Springer
    Publishing place London u.a.
    Publishing country Great Britain
    Document type Book
    Note Includes bibliographical references and index
    HBZ-ID HT013853960
    ISBN 1-85233-717-6 ; 978-1-85233-717-9
    Database Catalogue ZB MED Medicine, Health

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  6. Article: Bone Marrow Endothelial Cells Increase Prostate Cancer Cell Apoptosis in 3D Triculture Model of Reactive Stroma.

    Sablatura, Lindsey K / Tellman, Tristen V / Kim, Aemin / Farach-Carson, Mary C

    Biology

    2022  Volume 11, Issue 9

    Abstract: The bone marrow tumor microenvironment (BMTE) is a complex network of cells, extracellular matrix, and sequestered signaling factors that initially act as a hostile environment for disseminating tumor cells (DTCs) from the cancerous prostate. Three- ... ...

    Abstract The bone marrow tumor microenvironment (BMTE) is a complex network of cells, extracellular matrix, and sequestered signaling factors that initially act as a hostile environment for disseminating tumor cells (DTCs) from the cancerous prostate. Three-dimensional (3D) culture systems offer an opportunity to better model these complex interactions in reactive stroma, providing contextual behaviors for cancer cells, stromal cells, and endothelial cells. Using a new system designed for the triculture of osteoblastic prostate cancer (PCa) cells, stromal cells, and microvascular endothelial cells, we uncovered a context-specific pro-apoptotic effect of endothelial cells of the bone marrow different from those derived from the lung or dermis. The paracrine nature of this effect was demonstrated by observations that conditioned medium from bone marrow endothelial cells, but not from dermal or lung endothelial cells, led to PCa cell death in microtumors grown in 3D BMTE-simulating hydrogels. Analysis of the phosphoproteome by reverse phase protein analysis (RPPA) of PCa cells treated with conditioned media from different endothelial cells identified the differential regulation of pathways involved in proliferation, cell cycle regulation, and apoptosis. The findings from the RPPA were validated by western blotting for representative signaling factors identified, including forkhead box M1 (FOXM1; proliferation factor), pRb (cell cycle regulator), and Smac/DIABLO (pro-apoptosis) among treatment conditions. The 3D model presented here thus presents an accurate model to study the influence of the reactive BMTE, including stromal and endothelial cells, on the adaptive behaviors of cancer cells modeling DTCs at sites of bone metastasis. These findings in 3D culture systems can lead to a better understanding of the real-time interactions among cells present in reactive stroma than is possible using animal models.
    Language English
    Publishing date 2022-08-26
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2661517-4
    ISSN 2079-7737
    ISSN 2079-7737
    DOI 10.3390/biology11091271
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Book ; Online: Bone Resorption

    Bronner, Felix / Farach-Carson, Mary C. / Rubin, Janet

    2005  

    Author's details edited by Felix Bronner, Mary C Farach-Carson, Janet Rubin
    Keywords Endocrinology ; Internal medicine ; Orthopedics ; Rheumatology
    Language English
    Publisher Springer-Verlag London Limited
    Publishing place London
    Document type Book ; Online
    HBZ-ID TT050387301
    ISBN 978-1-85233-812-1 ; 978-1-8462-8016-0 ; 1-85233-812-1 ; 1-8462-8016-8
    DOI 10.1007/b136184
    Database ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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  8. Article: Flipping the Molecular Switch: Influence of Perlecan and Its Modifiers in the Tumor Microenvironment.

    Cruz, Lissette A / Tellman, Tristen V / Farach-Carson, Mary C

    Advances in experimental medicine and biology

    2020  Volume 1245, Page(s) 133–146

    Abstract: ... of the protein, primarily from C-terminal domains IV and V. These fragments influence cell adhesion, invasion ...

    Abstract The tumor microenvironment (TME) is rich in matrix components, growth factors, cytokines, and enzymatic modifiers that respond to changing conditions, to alter the fundamental properties of the tumor bed. Perlecan/HSPG2, a large, multi-domain heparan sulfate proteoglycan, is concentrated in the reactive stroma that surrounds tumors. Depending on its state in the TME, perlecan can either prevent or promote the progression of cancers to metastatic disease. Breast, prostate, lung, and renal cancers all preferentially metastasize to bone, a dense, perlecan-rich environment that is initially a "hostile" niche for cancer cells. Driven by inflammation, production of perlecan and its enzyme modifiers, which include matrix metalloproteinases (MMPs), sulfatases (SULFs), and heparanase (HPSE), increases in the reactive stroma surrounding growing and invading tumors. MMPs act upon the perlecan core protein, releasing bioactive fragments of the protein, primarily from C-terminal domains IV and V. These fragments influence cell adhesion, invasion, and angiogenesis. Sulfatases and heparanases act directly upon the heparan sulfate chains, releasing growth factors from reservoirs to reach receptors on the cancer cell surface. We propose that perlecan modifiers, by promoting the degradation of the perlecan-rich stroma, "flip the molecular switch" and convert the "hostile" stroma into a welcoming one that supports cancer dissemination and metastasis. Targeted therapies that prevent this molecular conversion of the TME should be considered as potential new therapeutics to limit metastasis.
    MeSH term(s) Extracellular Matrix Proteins/metabolism ; Heparan Sulfate Proteoglycans/metabolism ; Heparitin Sulfate/metabolism ; Humans ; Neoplasm Metastasis ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Neoplasms/pathology ; Tumor Microenvironment
    Chemical Substances Extracellular Matrix Proteins ; Heparan Sulfate Proteoglycans ; perlecan (143972-95-6) ; Heparitin Sulfate (9050-30-0)
    Language English
    Publishing date 2020-04-07
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 2214-8019 ; 0065-2598
    ISSN (online) 2214-8019
    ISSN 0065-2598
    DOI 10.1007/978-3-030-40146-7_6
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article: Modular Proteoglycan Perlecan/

    Martinez, Jerahme R / Dhawan, Akash / Farach-Carson, Mary C

    Genes

    2018  Volume 9, Issue 11

    Abstract: Heparan sulfate proteoglycan 2 ( ...

    Abstract Heparan sulfate proteoglycan 2 (
    Language English
    Publishing date 2018-11-16
    Publishing country Switzerland
    Document type Journal Article ; Review
    ZDB-ID 2527218-4
    ISSN 2073-4425
    ISSN 2073-4425
    DOI 10.3390/genes9110556
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Cleavage of the Perlecan-Semaphorin 3A-Plexin A1-Neuropilin-1 (PSPN) Complex by Matrix Metalloproteinase 7/Matrilysin Triggers Prostate Cancer Cell Dyscohesion and Migration.

    Tellman, Tristen V / Cruz, Lissette A / Grindel, Brian J / Farach-Carson, Mary C

    International journal of molecular sciences

    2021  Volume 22, Issue 6

    Abstract: The Perlecan-Semaphorin 3A-Plexin A1-Neuropilin-1 (PSPN) Complex at the cell surface of prostate cancer (PCa) cells influences cell-cell cohesion and dyscohesion. We investigated matrix metalloproteinase-7/matrilysin (MMP-7)'s ability to digest ... ...

    Abstract The Perlecan-Semaphorin 3A-Plexin A1-Neuropilin-1 (PSPN) Complex at the cell surface of prostate cancer (PCa) cells influences cell-cell cohesion and dyscohesion. We investigated matrix metalloproteinase-7/matrilysin (MMP-7)'s ability to digest components of the PSPN Complex in bone metastatic PCa cells using
    MeSH term(s) Cell Adhesion ; Cell Adhesion Molecules/metabolism ; Cell Line, Tumor ; Cell Movement ; Fluorescent Antibody Technique ; Humans ; Male ; Matrix Metalloproteinase 7/metabolism ; Models, Biological ; Nerve Tissue Proteins/metabolism ; Neuropilin-1/metabolism ; Prostatic Neoplasms/etiology ; Prostatic Neoplasms/metabolism ; Protein Binding ; Proteolysis
    Chemical Substances Cell Adhesion Molecules ; Nerve Tissue Proteins ; persephin ; plexin ; Neuropilin-1 (144713-63-3) ; MMP7 protein, human (EC 3.4.24.23) ; Matrix Metalloproteinase 7 (EC 3.4.24.23)
    Language English
    Publishing date 2021-03-22
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2019364-6
    ISSN 1422-0067 ; 1422-0067 ; 1661-6596
    ISSN (online) 1422-0067
    ISSN 1422-0067 ; 1661-6596
    DOI 10.3390/ijms22063218
    Database MEDical Literature Analysis and Retrieval System OnLINE

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