Publication: A magnetic three-dimensional levitated primary cell culture system for the development of secretory salivary gland-like organoids
Issued Date
2019-03-01
Resource Type
ISSN
19327005
19326254
19326254
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2-s2.0-85062784341
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Mahidol University
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SCOPUS
Bibliographic Citation
Journal of Tissue Engineering and Regenerative Medicine. Vol.13, No.3 (2019), 495-508
Suggested Citation
Joao N. Ferreira, Riasat Hasan, Ganokon Urkasemsin, Kiaw K. Ng, Christabella Adine, Sujatha Muthumariappan, Glauco R. Souza A magnetic three-dimensional levitated primary cell culture system for the development of secretory salivary gland-like organoids. Journal of Tissue Engineering and Regenerative Medicine. Vol.13, No.3 (2019), 495-508. doi:10.1002/term.2809 Retrieved from: https://repository.li.mahidol.ac.th/handle/20.500.14594/50861
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Title
A magnetic three-dimensional levitated primary cell culture system for the development of secretory salivary gland-like organoids
Abstract
© 2019 John Wiley & Sons, Ltd. Salivary gland (SG) hypofunction and oral dryness can be induced by radiotherapy for head and neck cancers or autoimmune disorders. These are common clinical conditions that involve loss of saliva-secreting epithelial cells. Several oral complications arise with SG hypofunction that interfere with routine daily activities such as chewing, swallowing, and speaking. Hence, there is a need for replacing these saliva-secreting cells. Recently, researchers have proposed to repair SG hypofunction via various cell-based approaches in three-dimensional (3D) scaffold-based systems. However, majority of the scaffolds used cannot be translated clinically due to the presence of non-human-based substrates. Herein, saliva-secreting organoids/mini-glands were developed using a new scaffold/substrate-free culture system named magnetic 3D levitation (M3DL), which assembles and levitates magnetized primary SG-derived cells (SGDCs), allowing them to produce their own extracellular matrices. Primary SGDCs were assembled in M3DL to generate SG-like organoids in well-established SG epithelial differentiation conditions for 7 days. After such culture time, these organoids consistently presented uniform spheres with greater cell viability and pro-mitotic cells, when compared with conventional salisphere cultures. Additionally, organoids formed by M3DL expressed SG-specific markers from different cellular compartments: acinar epithelial including adherens junctions (NKCC1, cholinergic muscarinic receptor type 3, E-cadherin, and EpCAM); ductal epithelial and myoepithelial (cytokeratin 14 and α-smooth muscle actin); and neuronal (β3-tubulin and vesicular acetylcholine transferase). Lastly, intracellular calcium and α-amylase activity assays showed functional organoids with SG-specific secretory activity upon cholinergic stimulation. Thus, the functional organoid produced herein indicate that this M3DL system can be a promising tool to generate SG-like mini-glands for SG secretory repair.