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Biomaterials-based strategies for salivary gland tissue regeneration

Tugba Ozdemir, Eric W. Fowler, Ying Hao, Anitha Ravikrishnan, Daniel A. Harrington, Robert L. Witt, Mary C. Farach-Carson, Swati Pradhan-Bhatt, Xinqiao Jia
2016 Biomaterials Science  
Reprinted from Pradhan-Bhatt et al., 2013 15 with permission. Fig. 6 6 Effect of substrate stiffness on the morphology and cell arrangement of ex vivo cultured embryonic gland.  ...  Pradhan et al. developed methods for isolating salivary gland acinar-like cell populations from tissue specimens harvested from patients undergoing head and neck surgery. 22 Primary human salivary gland  ... 
doi:10.1039/c5bm00358j pmid:26878077 pmcid:PMC4803517 fatcat:minwgak4fzb3faqp7ct2q2pioy

Bottom-up assembly of salivary gland microtissues for assessing myoepithelial cell function

Tugba Ozdemir, Padma Pradeepa Srinivasan, Daniel R. Zakheim, Daniel A. Harrington, Robert L. Witt, Mary C. Farach-Carson, Xinqiao Jia, Swati Pradhan-Bhatt
2017 Biomaterials  
Myoepithelial cells are flat, stellate cells present in exocrine tissues including the salivary glands. While myoepithelial cells have been studied extensively in mammary and lacrimal gland tissues, less is known of the function of myoepithelial cells derived from human salivary glands. Several groups have isolated tumorigenic myoepithelial cells from cancer specimens, however, only one report has demonstrated isolation of normal human salivary myoepithelial cells needed for use in salivary
more » ... d tissue engineering applications. Establishing a functional organoid model consisting of myoepithelial and secretory acinar cells is therefore necessary for understanding the coordinated action of these two cell types in unidirectional fluid secretion. Here, we developed a bottom-up approach for generating salivary gland microtissues using primary human salivary myoepithelial cells (hSMECs) and stem/progenitor cells (hS/PCs) isolated from normal salivary gland tissues. Phenotypic characterization of isolated hSMECs confirmed that a myoepithelial cell phenotype consistent with that from other exocrine tissues was maintained over multiple passages of tissue culture. Additionally, hSMECs secreted basement membrane proteins, expressed adrenergic and cholinergic neurotransmitter receptors, and released intracellular calcium [Ca 2+ i ] in response to parasympathetic agonists. In a collagen I contractility assay, activation of contractile machinery was observed in isolated hSMECs treated with parasympathetic agonists. Recombination of hSMECs with assembled hS/PC spheroids in a microwell system was used to create microtissues resembling secretory complexes of the salivary gland. We conclude that the engineered salivary gland microtissue complexes provide a physiologically relevant model for both mechanistic studies and as a building block for the successful engineering of the salivary gland for restoration of salivary function in patients suffering from hyposalivation.
doi:10.1016/j.biomaterials.2017.07.022 pmid:28734180 pmcid:PMC5561745 fatcat:qlv3upl6ezh6hakkr4dalewq3q

A novel in vivo model for evaluating functional restoration of a tissue-engineered salivary gland

Swati Pradhan-Bhatt, Daniel A. Harrington, Randall L. Duncan, Mary C. Farach-Carson, Xinqiao Jia, Robert L. Witt
2013 The Laryngoscope  
Objectives/Hypothesis-To create a novel model for development of a tissue-engineered salivary gland from human salivary gland cells that retain progenitor cell markers useful for treatment of radiation-induced xerostomia. Study Design-A 3D hyaluronic acid (HA)-based hydrogel scaffold was used to encapsulate primary human salivary gland cells and to obtain organized acini-like spheroids. Hydrogels were implanted into rat models and cell viability and receptor expression were evaluated. Methods-A
more » ... parotid gland surgical resection model for xenografting was developed. Salivary cells loaded in HA hydrogels formed spheroids in vitro and were implanted in the ¾ resected parotid bed of athymic rats. Implants were removed after one week and analyzed for spheroid viability and phenotype retention. Results-Spheroids in 3D stained positive for HA receptors CD168/RHAMM and CD44, which is also a progenitor cell marker. The parotid gland ¾ resection model was well-tolerated by rodent hosts and the salivary cell/hydrogel scaffolds were adherent to the remaining parotid gland, with no obvious signs of inflammation. A majority of human cells in the extracted hydrogels demonstrated robust expression of CD44. Conclusions-A 3D HA-based hydrogel scaffold that supported long-term culture of salivary gland cells into organized spheroids was established. An in vivo salivary gland resection model was developed that allowed for integration of the 3D HA hydrogel scaffold with the existing glandular parenchyma. The expression of CD44 among salivary cultures may partially explain their regenerative potential and the expression of CD168/RHAMM along with CD44 may aid the development of these 3D spheroids into regenerated salivary glands.
doi:10.1002/lary.24297 pmid:23832678 pmcid:PMC4022597 fatcat:ofjvqxft4ngetlnycikhknr6ma

Tuning Hydrogel Properties to Promote the Assembly of Salivary Gland Spheroids in 3D

Tugba Ozdemir, Eric W. Fowler, Shuang Liu, Daniel A. Harrington, Robert L. Witt, Mary C. Farach-Carson, Swati Pradhan-Bhatt, Xinqiao Jia
2016 ACS Biomaterials Science & Engineering  
Current treatments for chronic xerostomia, or "dry mouth", do not offer long-term therapeutic benefits for head and neck cancer survivors previously treated with curative radiation. Towards the goal of creating tissue-engineered constructs for the restoration of salivary gland functions, we developed new hyaluronic acid (HA)-based hydrogels using thiolated HA (HA-SH) and acrylated HA (HA-AES) with a significant molecular weight mismatch. Four hydrogel formulations with varying HA concentration,
more » ... (1-2.4 wt%) and thiol/acrylate ratios (2/1 to 36/1) and elastic moduli (G': 35 to 1897 Pa, 2 h post-mixing) were investigated. In our system, thiol/acrylate reaction was initiated rapidly upon mixing of HA-SH/HA-AES to establish thioether crosslinks with neighboring ester groups, and spontaneous sulfhydryl oxidation occurred slowly over several days to install a secondary network. The concurrent reactions cooperatively create a cell-permissive network to allow for cell expansion and aggregation. Multicellular spheroids formed readily from a robust ductal epithelial cell line (Madin-Darby Canine Kidney, MDCK cells) in all hydrogel formulations investigated. Primary salivary human stem/progenitor cells (hS/PCs), on the other hand, are sensitive to the synthetic extracellular environment, and organized acini-like structures Supporting information: Synthesis and characterization of hydrogel precursors, antibody information, flow cytometry characterization of cell surface CD44, fluorescent staining of cell surface thiol, 6-h in situ rheology of DRC18, appearance of DRC constructs after 27 days of culture, immunostaining for K5 and K14 on hS/PC spheroids grown in DRC2 and DRC4, F-actin staining of hS/PCs grown in HA-SH/HA-AM and 3D reconstructed confocal image of hS/PC spheroid. with an average diameter of 50 µm were obtained only in gels with G' ≤ 216 Pa and a thiol/ acrylate ratio ≥18. The spheroid size and size distribution were dependent on the HA content in the hydrogel. Cells in hS/PC spheroids formed tight junctions (occludin), remained viable and proliferative, secreted structural proteins (collagen IV and laminin) found in the basement membrane and maintained key stem/progenitor markers. We conclude that incorporation of timedependent, dynamic features into a covalently crosslinked HA network produces an adaptable hydrogel framework that promotes hS/PC assembly and supports early aspects of salivary morphogenesis, key to reconstitution of a fully functional implantable salivary gland.
doi:10.1021/acsbiomaterials.6b00419 pmid:27990487 pmcid:PMC5155608 fatcat:qbjduemkhbbmnejrvps2cfjfmi

Implantable Three-Dimensional Salivary Spheroid Assemblies Demonstrate Fluid and Protein Secretory Responses to Neurotransmitters

Swati Pradhan-Bhatt, Daniel A. Harrington, Randall L. Duncan, Xinqiao Jia, Robert L. Witt, Mary C. Farach-Carson
2013 Tissue Engineering. Part A  
ACh, acetylcholine; 2.5D, 2.5-dimensional; 3D, three-dimensional. 1618 PRADHAN-BHATT ET AL. and Xian Xu for performing rheological characterization of the hydrogels. We thank Dr.  ...  The image on the right shows a representative area measurement. 1616 PRADHAN-BHATT ET AL.  ...  Over 50% of the cells in the treated samples displayed granules. 1614 PRADHAN-BHATT ET AL.  ... 
doi:10.1089/ten.tea.2012.0301 pmid:23442148 pmcid:PMC3665323 fatcat:k7jk5242krcenmi2g6gnvrxjjq

Primary Salivary Human Stem/Progenitor Cells Undergo Microenvironment-Driven Acinar-Like Differentiation in Hyaluronate Hydrogel Culture

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
2016 Stem Cells Translational Medicine  
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
more » ... ogenic rejection. Here, we report an expandable population of primary salivary human stem/ progenitor cells (hS/PCs) that can be reproducibly and scalably isolated and propagated from tissue biopsies. These cells have increased expression of progenitor markers (K5, K14, MYC, ETV4, ETV5) compared with differentiation markers of the parotid gland (acinar: MIST1/BHLHA15 and AMY1A; ductal: K19 and TFCP2L1). Isolated hS/PCs grown in suspension formed primary and secondary spheres and could be maintained in long-term 3D hydrogel culture. When grown in a customized 3D modular hyaluronate-based hydrogel system modified with bioactive basement membranederived peptides, levels of progenitor markers, indices of proliferation, and viability of hS/PCs were enhanced. When appropriate microenvironmental cues were provided in a controlled manner in 3D, such as stimulation with b-adrenergic and cholinergic agonists, hS/PCs differentiated into an acinarlike lineage, needed for saliva production. We conclude that the stem/progenitor potential of adult hS/PCs isolated without antigenic sorting or clonal expansion in suspension, combined with their ability to differentiate into specialized salivary cell lineages in a human-compatible culture system, makes them ideal for use in 3D bioengineered salivary gland applications. STEM CELLS TRANSLATIONAL MEDICINE 2016;5:1-11 SIGNIFICANCE Therapeutic irradiation for locally invasive head and neck cancers often leads to xerostomia or severe dry mouth, which greatly impairs quality of life. With current remedies being unsatisfactory, engineering an implantable salivary gland capable of restoring salivary functions of these patients is a promising solution. A major milestone toward salivary gland engineering is the identification and isolation of an expandable population of adult salivary human stem/progenitor cells (hS/PCs). Here we report a population of salivary hS/PCs that can be reliably isolated in scalable quantities, maintained long-term in two-dimensional/three-dimensional (3D) culture, and used to produce a variety of salivary epithelial cell types for use in our human-compatible, 3D engineered hydrogel model. Our ultimate goal is to use these cells to regenerate a functional autologous implantable salivary gland fully capable of reversing xerostomia.
doi:10.5966/sctm.2016-0083 pmid:28170182 pmcid:PMC5442728 fatcat:75ssto3gzjbhtlwfbe6zcszniq

Immunosuppressed Miniswine as a Model for Testing Cell Therapy Success: Experience With Implants of Human Salivary Stem/Progenitor Cell Constructs

Danielle Wu, Isabelle M. A. Lombaert, Maximilien DeLeon, Swati Pradhan-Bhatt, Robert L Witt, Daniel Anton Harrington, Mark G Trombetta, Michael J Passineau, Mary C. Farach-Carson
2021 Frontiers in Molecular Biosciences  
., 1991; Pradhan-Bhatt et al., 2013) .  ...  In previous work, we (Pradhan-Bhatt et al., 2014) and others (Yoo et al., 2014; Mitroulia et al., 2019) used rats and mice, both irradiated and non-irradiated, for testing cell-based regeneration therapies  ... 
doi:10.3389/fmolb.2021.711602 pmid:34660692 pmcid:PMC8516353 fatcat:c3awgsyfqzhjfpmc2e24oykma4

Table of Contents CISPSSE 2020

2020 2020 International Conference on Computational Intelligence for Smart Power System and Sustainable Energy (CISPSSE)  
Reduction in NPC Multilevel Inverter by SVPWM using gh- Coordinate System Sesadribhusan Sahoo and Irfan Ahmed 61 258009 Speed Range Improvement of Induction Generator for wind Power Applications Swati  ...  Management with Reduced Co-Channel Interference in WLAN Prasanta Kumar Swain and Shashi Bhusan Panda 64 258012 SMS-Based Offline Mobile Device Security System Royston Furtado, Atharva More, Jay Bhatt  ... 
doi:10.1109/cispsse49931.2020.9212218 fatcat:qfhqrkqrizexbfyc774yjwknrq

Detailed Technical Programme Schedule

2020 2020 Sixth International Conference on Parallel, Distributed and Grid Computing (PDGC)  
Shikha Mundra 07.1: Evolving Technologies for Computing and Data Analytics Presenter Based Parallel Prefix Speculative Adder for Garima Thakur Gourav Bathla Tende Ivo Sake Ajit Singh Swati  ...  Cloud Computing 02.2: Parallel, Distributed and Grid Computing Applications and Technologies Presenter Dammu Sowjanya and Supriya Yamjala Suman De Meghna Dhalaria Jessicaa Singh Pandaba Pradhan  ... 
doi:10.1109/pdgc50313.2020.9315322 fatcat:4ndwytytovb7xkntz7bmaurj6a

Table of Contents

2020 2020 IEEE International Conference on Electronics, Computing and Communication Technologies (CONECCT)  
Trivedi, Anmol Nijhawan, Santanu Tribikram Pradhan Shashikant Deepak, Vrushali Khorgade and Seth, Leo Jackson John and B. N. Dr.  ...  Srikanth P C Amit Mankodi, Amit Bhatt, Bhaskar Chaudhury, Rajat Kumar and Aditya Kriti Sundar Das and Zala Abhimanyusinh Mansi Malhotra, Mehak Ganjoo, Supriya Kelkar, Shreya Kulkarni and Sneha Paranjape  ... 
doi:10.1109/conecct50063.2020.9198692 fatcat:cx7f3usgtbazbnj4g5fxl7yzba

FANTOM5 CAGE profiles of human and mouse samples

Shuhei Noguchi, Takahiro Arakawa, Shiro Fukuda, Masaaki Furuno, Akira Hasegawa, Fumi Hori, Sachi Ishikawa-Kato, Kaoru Kaida, Ai Kaiho, Mutsumi Kanamori-Katayama, Tsugumi Kawashima, Miki Kojima (+166 others)
2017 Scientific Data  
In the FANTOM5 project, transcription initiation events across the human and mouse genomes were mapped at a single base-pair resolution and their frequencies were monitored by CAGE (Cap Analysis of Gene Expression) coupled with single-molecule sequencing. Approximately three thousands of samples, consisting of a variety of primary cells, tissues, cell lines, and time series samples during cell activation and development, were subjected to a uniform pipeline of CAGE data production. The analysis
more » ... pipeline started by measuring RNA extracts to assess their quality, and continued to CAGE library production by using a robotic or a manual workflow, single molecule sequencing, and computational processing to generate frequencies of transcription initiation. Resulting data represents the consequence of transcriptional regulation in each analyzed state of mammalian cells. Non-overlapping peaks over the CAGE profiles, approximately 200,000 and 150,000 peaks for the human and mouse genomes, were identified and annotated to provide precise location of known promoters as well as novel ones, and to quantify their activities.
doi:10.1038/sdata.2017.112 pmid:28850106 pmcid:PMC5574368 fatcat:cel5hhhtardinak67mbl2okvhe

Program Schedule

2021 2021 5th International Conference on Information Systems and Computer Networks (ISCON)  
Kumar Real-Time Commuincation based IoT enabled Smart Sewage Workers Safety Monitoring System 614 Dhirendra Prasad Yadav Feature Fusion based Deep Learning method for Leukemia cell classification 615 Swati  ...  Dinanath Prasad and Sanjeev Kumar Ojha A Strategic Technique for Transient Stability Enhancement by using Coordinated Control of SVC and Optimal Reclosure of Circuit Breaker 461 Srashti Rastogi, Priyanka Bhatt  ... 
doi:10.1109/iscon52037.2021.9702510 fatcat:cx6yd6pfwvbslc5p7u546suq4m

Border patrol: Insights into the unique role of perlecan/heparan sulfate proteoglycan 2 at cell and tissue borders

Mary C. Farach-Carson, Curtis R. Warren, Daniel A. Harrington, Daniel D. Carson
2014 Matrix Biology  
Swati Pradhan-Bhatt. Table 1 1 Perlecan binding factors involved in tissue structure and function.  ...  et al., 2010; Pradhan-Bhatt et al., 2013) .  ... 
doi:10.1016/j.matbio.2013.08.004 pmid:24001398 pmcid:PMC3938997 fatcat:mssavphw7nfnddsagdztrub7da

Roadmap for Scaling Trees Outside Forests in India: Learnings from Select States on Policy Incentives, Enabling Conditions, and Barriers

Marie Duraisami, Ruchika Singh, Swati Chaliha
2022 World Resources Institute  
Swati Chaliha is a former consultant with the Sustainable Landscapes and Restoration program at WRI India. Ruchika Note: INR = Indian rupee.  ...  Even among established wood-based industries, such as furniture, plywood, handicrafts, etc., value chains remain informal or "unorganized" (NCCF 2021; Bhatt 2021) .  ... 
doi:10.46830/wriwp.21.00050 fatcat:vsn4tezymzecjawr3wjlxa2zea

Finger Millet: A "Certain" Crop for an "Uncertain" Future and a Solution to Food Insecurity and Hidden Hunger under Stressful Environments

Sanjay Mohan Gupta, Sandeep Arora, Neelofar Mirza, Anjali Pande, Charu Lata, Swati Puranik, J. Kumar, Anil Kumar
2017 Frontiers in Plant Science  
Studies conducted by Pradhan et al. (2010) on male and female diabetic patients spread across different rural and urban locations, also showed that the glucose level was maintained after consuming multigrain  ...  gene Stress tolerance Reference EcDehydrin7 Finger millet Over expression of EcDehydrin7 induce abiotic stress tolerances Singh R.K. et al., 2014 Ec-apx1 Finger millet Expression increased under drought Bhatt  ... 
doi:10.3389/fpls.2017.00643 pmid:28487720 pmcid:PMC5404511 fatcat:czn7zr56mjcmpfaebfs2jygaqu
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