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salivary gland, stem cell

Zhifa Wang, Zhaoyu Ju, Longlong He, Zhijin Li, Yanpu Liu, Bin Liu
PURPOSE: In a previous study, the authors verified the protective efficacy of adipose-derived stem cells (ADSCs) on the prevention of salivary gland (SG) damage induced by irradiation in mice. As a critical step before implementation in clinical practice, the present study investigated the protective effect of ADSCs in a miniature pig SG model, because miniature pigs share many characteristics with humans. MATERIALS AND METHODS: Third-passage autologous ADSCs at a concentration of 4 × 10(6) cells/mL were transplanted by intraglandular injection into parotid glands (PGs) immediately after local irradiation at a single dose of 20 Gy...
August 16, 2016: Journal of Oral and Maxillofacial Surgery
Pouya Amrollahi, Brinda Shah, Amir Seifi, Lobat Tayebi
Although human mouth benefits from remarkable mechanical properties, it is very susceptible to traumatic damages, exposure to microbial attacks, and congenital maladies. Since the human dentition plays a crucial role in mastication, phonation and esthetics, finding promising and more efficient strategies to reestablish its functionality in the event of disruption has been important. Dating back to antiquity, conventional dentistry has been offering evacuation, restoration, and replacement of the diseased dental tissue...
December 1, 2016: Materials Science & Engineering. C, Materials for Biological Applications
E E Joo, I M A Lombaert, K M Yamada
Cells engage in bidirectional communication with their surroundings. This reciprocal dialogue between cells and their cellular microenvironments often governs the maintenance and differentiation of stem/progenitor cells. Here, the authors present evidence that in developing salivary gland explants, a single posttranslational change in microtubules in mesenchymal cells alters the mesenchymal microenvironment and promotes the maintenance and differentiation of a subset of epithelial progenitor cells that impairs branching morphogenesis...
August 19, 2016: Journal of Dental Research
Padma Pradeepa Srinivasan, Vaishali N Patel, Shuang Liu, Daniel A Harrington, Matthew P Hoffman, Xinqiao Jia, Robert L Witt, Mary C Farach-Carson, Swati Pradhan-Bhatt
: : Radiotherapy for head and neck cancer often has undesirable effects on salivary glands that lead to xerostomia or severe dry mouth, which can increase oral infections. Our goal is to engineer functional, three-dimensional (3D) salivary gland neotissue for autologous implantation to provide permanent relief. An immediate need exists to obtain autologous adult progenitor cells as the use of embryonic and induced pluripotent stem cells potentially pose serious risks such as teratogenicity and immunogenic rejection...
August 18, 2016: Stem Cells Translational Medicine
Lorenz Kadletz, Klaus Aumayr, Gregor Heiduschka, Sven Schneider, Elisabeth Enzenhofer, Claudia Lill
Salivary gland carcinomas are a rare malignancy. Therefore, little is known about biomarkers and cancer stem cells in salivary gland malignancies. Double cortin-like kinase 1 (DCLK1) is a promising therapeutic target and cancer stem cell marker, predominantly investigated in pancreatic and colorectal cancer. The purpose of this study was to investigate the expression of DCLK1 in major and minor salivary gland carcinomas and its influence on survival. We examined a total of 80 patients with major or minor salivary gland cancer in this retrospective study...
July 28, 2016: European Archives of Oto-rhino-laryngology
Isabelle Lombaert, Mohammad M Movahednia, Christabella Adine, Joao N Ferreira
The human salivary gland (SG) has an elegant architecture of epithelial acini, connecting ductal branching structures, vascular and neuronal networks that together function to produce and secrete saliva. This review focuses on the translation of cell- and tissue-based research toward therapies for patients suffering from SG hypofunction and related dry mouth syndrome (xerostomia), as a consequence of radiation therapy or systemic disease. We will broadly review the recent literature and discuss the clinical prospects of stem/progenitor cell and tissue-based therapies for SG repair and/or regeneration...
July 12, 2016: Stem Cells
Douglas M Guimarães, Luciana O Almeida, Manoela D Martins, Kristy A Warner, Alan R S Silva, Pablo A Vargas, Fabio D Nunes, Cristiane H Squarize, Jacques E Nör, Rogerio M Castilho
Mucoepidermoid carcinoma (MEC) is the most common malignancy of salivary glands. The response of MEC to chemotherapy is unpredictable, and recent advances in cancer biology suggest the involvement of cancer stem cells (CSCs) in tumor progression and chemoresistance and radioresistance phenotype. We found that histone acetyltransferase inhibitors (HDACi) were capable of disrupting CSCs in MEC. Furthermore, administration of HDACi prior to Cisplatin (two-hit approach) disrupts CSCs and sensitizes tumor cells to Cisplatin...
June 7, 2016: Oncotarget
Elizabeth T Ables, Grace H Hwang, Danielle S Finger, Taylor D Hinnant, Daniela Drummond-Barbosa
Multiple aspects of Drosophila oogenesis, including germline stem cell activity, germ cell differentiation, and follicle survival, are regulated by the steroid hormone ecdysone. While the transcriptional targets of ecdysone signaling during development have been studied extensively, targets in the ovary remain largely unknown. Early studies of salivary gland polytene chromosomes led to a model in which ecdysone stimulates a hierarchical transcriptional cascade, wherein a core group of ecdysone-sensitive transcription factors induce tissue-specific responses by activating secondary branches of transcriptional targets...
2016: G3: Genes—Genomes—Genetics
Chun Yi, Bin-Bin Li, Chuan-Xiang Zhou
Salivary adenoid cystic carcinoma (AdCC) is known for its high propensity to invade and metastasize. Bmi-1 acts as an oncogene by controlling cell cycle and self-renewal of adult stem cells, and its overexpression correlates with metastasis and poor prognosis in several cancers. Epithelial-mesenchymal transition (EMT) plays a central role in cancer metastasis. A key step in EMT is the down-regulation of E-cadherin that can be repressed by the transcriptional factors, such as Snail and Slug. In the present study, we investigated Bmi-1, Snail, Slug, and E-cadherin expression by immunohistochemistry in 102 patients with AdCC and analyzed statistically whether their expression correlated with clinicopathologic factors and prognosis...
June 2016: Annals of Diagnostic Pathology
Su Han Lum, Denise Bonney, Edmund Cheesman, Neville B Wrignt, Stephen Hughes, Robert Wynn
Idiopathic CD4+ lymphocytopenia and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are rare diseases in children. We report the first case of a child with STK4-mutated CD4+ lymphocytopenia who developed Epstein-Barr virus associated MALT lymphoma arising in the salivary gland. The child achieved complete remission with rituximab, and her immunodeficiency was cured by haematopoietic stem cell transplantation. The child remained well 24 months post transplantation.
September 2016: Pediatric Blood & Cancer
Maria Fernanda Setúbal Destro Rodrigues, Bruno Tavares Sedassari, Carina Magalhães Esteves, Nathália Paiva de Andrade, Albina Altemani, Suzana Cantanhede Orsini Machado de Sousa, Fabio Daumas Nunes
BACKGROUND: Mucoepidermoid carcinoma (MEC) is the most common salivary gland malignancy and is successfully treated by surgery and radiation. However, some patients have recurrent tumours and in these cases, few treatments options are available. Cancer stem cells (CSC) have been observed and isolated from different solid tumours based on the expression of stem cell markers. These cells are associated with tumour initiation, progression as well as treatment resistance. In this study, the expression of stem cell markers CD44, Bmi1, Oct4 and Nanog was evaluated in non-neoplastic salivary tissue and in MEC...
May 1, 2016: Journal of Oral Pathology & Medicine
Peter W Nagle, Nynke A Hosper, Emily M Ploeg, Marc-Jan van Goethem, Sytze Brandenburg, Johannes A Langendijk, Roland K Chiu, Robert P Coppes
PURPOSE: A reduction in the dose, irradiated volume, and sensitivity of, in particular, normal tissue stem cells is needed to advance radiation therapy. This could be obtained with the use of particles for radiation therapy. However, the radiation response of normal tissue stem cells is still an enigma. Therefore, in the present study, we developed a model to investigate the in vitro response of stem cells to particle irradiation. METHODS AND MATERIALS: We used the immortalized human salivary gland (HSG) cell line resembling salivary gland (SG) cells to translate the radiation response in 2-dimensional (2D) to 3-dimensional (3D) conditions...
May 1, 2016: International Journal of Radiation Oncology, Biology, Physics
Bo Hai, Qingguo Zhao, Lizheng Qin, Dharanipathy Rangaraj, Veera R Gutti, Fei Liu
Irreversible hypofunction of salivary glands is common in head and neck cancer survivors treated with radiotherapy and can only be temporarily relieved with current treatments. We found in an inducible sonic hedgehog (Shh) transgenic mouse model that transient activation of the Hedgehog pathway after irradiation rescued salivary gland function in males by preserving salivary stem/progenitor cells and parasympathetic innervation. To translate these findings into feasible clinical application, we evaluated the effects of Shh gene transfer to salivary glands of wild-type mice on irradiation-induced hyposalivation...
May 2016: Human Gene Therapy
M Kwak, N Alston, S Ghazizadeh
Salivary glands have an essential secretory function for maintaining oral and overall health. The epithelial compartment of the gland is composed of several highly specialized cell types that cooperate to secrete and deliver saliva to the oral cavity. The mouse submandibular gland has been used as a model for major salivary glands in human. The secretory complex in this model is composed of 2 secretory compartments, including acini and granular ducts connected by intercalated ducts. Contractile myoepithelial cells surround the secretory complex to facilitate salivary flow...
July 2016: Journal of Dental Research
Sarah Pringle, Martti Maimets, Marianne van der Zwaag, Monique A Stokman, Djoke van Gosliga, Erik Zwart, Max J H Witjes, Gerald de Haan, Ronald van Os, Rob P Coppes
Adult stem cells are often touted as therapeutic agents in the regenerative medicine field, however data detailing both the engraftment and functional capabilities of solid tissue derived human adult epithelial stem cells is scarce. Here we show the isolation of adult human salivary gland (SG) stem/progenitor cells and demonstrate at the single cell level in vitro self-renewal and differentiation into multilineage organoids. We also show in vivo functionality, long-term engraftment, and functional restoration in a xenotransplantation model...
March 2016: Stem Cells
Daan Nevens, Sandra Nuyts
Xerostomia is an important complication following radiotherapy (RT) for head and neck cancer. Current treatment approaches are insufficient and can only temporarily relieve symptoms. New insights into the physiopathology of radiation-induced xerostomia might help us in this regard. This review discusses the current knowledge of salivary gland stem cells in radiation-induced xerostomia and their value in the prevention and treatment of this complication. Salivary gland stem cell transplantation, bone marrow-derived cell mobilization, molecular regulation of parotid stem cells, stem cell sparing RT, and adaptive RT are promising techniques that are discussed in this study...
June 2016: Cancer Medicine
Tugba Ozdemir, Eric W Fowler, Ying Hao, Anitha Ravikrishnan, Daniel A Harrington, Robert L Witt, Mary C Farach-Carson, Swati Pradhan-Bhatt, Xinqiao Jia
The salivary gland is a complex, secretory tissue that produces saliva and maintains oral homeostasis. Radiation induced salivary gland atrophy, manifested as "dry mouth" or xerostomia, poses a significant clinical challenge. Tissue engineering recently has emerged as an alternative, long-term treatment strategy for xerostomia. In this review, we summarize recent efforts towards the development of functional and implantable salivary glands utilizing designed polymeric substrates or synthetic matrices/scaffolds...
April 2016: Biomaterials Science
Miyuki Kawakami, Hiroshi Ishikawa, Akira Tanaka, Izumi Mataga
Atrophy or hypofunction of the salivary gland because of aging or disease leads to hyposalivation that affects patient quality of life by causing dry mouth, deterioration of mastication/deglutition, and poor oral hygiene status. Current therapy for atrophy or hypofunction of the salivary gland in clinical practice focuses on symptom relief using drugs and artificial saliva; therefore, there is still a need to develop new therapies. To investigate potential novel therapeutic targets, we induced the differentiation of salivary gland cells by co-culturing human adipose-derived stem cells isolated from buccal fat pads (hBFP-ASCs) with human salivary-gland-derived fibroblasts (hSG-fibros)...
July 2016: Human Cell
Martti Maimets, Cecilia Rocchi, Reinier Bron, Sarah Pringle, Jeroen Kuipers, Ben N G Giepmans, Robert G J Vries, Hans Clevers, Gerald de Haan, Ronald van Os, Robert P Coppes
Adult stem cells are the ultimate source for replenishment of salivary gland (SG) tissue. Self-renewal ability of stem cells is dependent on extrinsic niche signals that have not been unraveled for the SG. The ductal compartment in SG has been identified as the location harboring stem cells. Here, we report that rare SG ductal EpCAM(+) cells express nuclear β-catenin, indicating active Wnt signaling. In cell culture experiments, EpCAM(high) cells respond potently to Wnt signals stimulating self-renewal and long-term expansion of SG organoids, containing all differentiated SG cell types...
January 12, 2016: Stem Cell Reports
P García-Gallastegui, J Luzuriaga, M Aurrekoetxea, V Baladrón, M J Ruiz-Hidalgo, J J García-Ramírez, J Laborda, F Unda, G Ibarretxe
DLK1 (PREF1, pG2, or FA1) is a transmembrane and secreted protein containing epidermal growth factor-like repeats. Dlk1 expression is abundant in many tissues during embryonic and fetal development and is believed to play an important role in the regulation of tissue differentiation and fetal growth. After birth, Dlk1 expression is abolished in most tissues but is possibly reactivated to regulate stem cell activation and responses to injury. We have recently reported that DLK1 regulates many aspects of salivary gland organogenesis...
June 2016: Cell and Tissue Research
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