Formation of post-confluence structure in human parotid gland acinar cells on PLGA through regulation of E-cadherin

Chan, Yen-Hui; Huang, Tsung‐Wei; Chou, Ya-Shuan; Hsu, Shu‐Han; Su, Wei‐Fang; Lou, Pei‐Jen; Young, Tai‐Horng

doi:10.1016/j.biomaterials.2011.09.060

Cited by 16 publications

(16 citation statements)

References 29 publications

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“…Groups that reported salivary acini-like structures or spheroids growing in 2D or 2.5D [34][35][36][37][38] obtained less wellorganized salivary structures compared to those seen in 3D cultures.…”

Section: D Salivary Assemblies Respond To Neurotransmittersmentioning

confidence: 99%

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

Pradhan-Bhatt

Harrington

Duncan

et al. 2013

Tissue Engineering Part A

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Radiation treatment in patients with head and neck tumors commonly results in hyposalivation and xerostomia due to the loss of fluid-secreting salivary acinar cells. Patients develop susceptibility to oral infections, dental caries, impaired speech and swallowing, reducing the quality of life. Clinical management is largely unsatisfactory. The development of a tissue-engineered, implantable salivary gland will greatly benefit patients suffering from xerostomia. This report compares the ability of a 2.5-dimensional (2.5D) and a three-dimensional (3D) hyaluronic acid (HA)-based culture system to support functional salivary units capable of producing fluid and phenotypic proteins. Parotid cells seeded on 2.5D, as well as those encapsulated in 3D HA hydrogels, selfassembled into acini-like structures and expressed functional neurotransmitter receptors. Structures in 3D hydrogels merged to form organized 50 mm spheroids that could be maintained in culture for over 100 days and merged to form structures over 500 mm in size. Treatment of acini-like structures with the b-adrenergic agonists norepinephrine or isoproterenol increased granule production and a-amylase staining in treated structures, demonstrating regain of protein secretion. Upon treatment with the M3 muscarinic agonist acetylcholine, acinilike structures activated the fluid production pathway by increasing intracellular calcium levels. The increase in intracellular calcium seen in structures in the 3D hydrogel culture system was more robust and prolonged than that in 2.5D. To compare the long-term survival and retention of acini-like structures in vivo, cell-seeded 2.5D and 3D hydrogels were implanted into an athymic rat model. Cells in 2.5D failed to maintain organized acinilike structures and dispersed in the surrounding tissue. Encapsulated cells in 3D retained their spheroid structure and structural integrity, along with the salivary biomarkers and maintained viability for over 3 weeks in vivo. This report identifies a novel hydrogel culture system capable of creating and maintaining functional 3D salivary spheroid structures for long periods in vitro that regain both fluid and protein secreting functions and are suitable for tissue restoration.

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Section: D Salivary Assemblies Respond To Neurotransmittersmentioning

confidence: 99%

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

Pradhan-Bhatt

Harrington

Duncan

et al. 2013

Tissue Engineering Part A

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“…However, these post-confluence 3D structures are fairly disorganized, potentially because of the absence of basement membrane signals. 17 …”

Section: Biomaterials Strategymentioning

confidence: 99%

Biomaterials-based strategies for salivary gland tissue regeneration

et al. 2016

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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. Although the in vitro engineering of a complex implantable salivary gland is technically challenging, opportunities exist for multidisciplinary teams to harvest the regenerative potential of stem/progenitor cells found in the adult glands and combine them with biomimetic and cell-instructive materials to assemble implantable tissue modules.

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“…Additionally, Matrigel is nonimplantable in humans. Other approaches have explored the use of flat synthetic and/or natural substrates to organize salivary gland cells into a monolayer [11–13]. Salivary gland cells grown on flat polymeric substrates often fail to assemble tight junctions, which are needed for directional secretion of saliva [14–16], and are unable to form a complex 3-D branching structure, a requirement for producing sufficient surface area to produce adequate amounts of saliva [17].…”

Section: Introductionmentioning

confidence: 99%

Salivary gland cell differentiation and organization on micropatterned PLGA nanofiber craters

et al. 2013

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There is a need for an artificial salivary gland as a long-term remedy for patients suffering from salivary hypofunction, a leading cause of chronic xerostomia (dry mouth). Current salivary gland tissue engineering approaches are limited in that they either lack sufficient physical cues and surface area needed to facilitate epithelial cell differentiation, or they fail to provide a mechanism for assembling an interconnected branched network of cells. We have developed highly-ordered arrays of curved hemispherical “craters” in polydimethylsiloxane (PDMS) using wafer-level integrated circuit (IC) fabrication processes, and lined them with electrospun poly-lactic-co-glycolic acid (PLGA) nanofibers, designed to mimic the three-dimensional (3-D) in vivo architecture of the basement membrane surrounding spherical acini of salivary gland epithelial cells. These micropatterned scaffolds provide a method for engineering increased surface area and were additionally investigated for their ability to promote cell polarization. Two immortalized salivary gland cell lines (SIMS, ductal and Par-C10, acinar) were cultured on fibrous crater arrays of various radii and compared with those grown on flat PLGA nanofiber substrates, and in 3-D Matrigel. It was found that by increasing crater curvature, the average height of the cell monolayer of SIMS cells and to a lesser extent, Par-C10 cells, increased to a maximum similar to that seen in cells grown in 3-D Matrigel. Increasing curvature resulted in higher expression levels of tight junction protein occludin in both cell lines, but did not induce a change in expression of adherens junction protein Ecadherin. Additionally, increasing curvature promoted polarity of both cell lines, as a greater apical localization of occludin was seen in cells on substrates of higher curvature. Lastly, substrate curvature increased expression of the water channel protein aquaporin-5 (Aqp-5) in Par-C10 cells, suggesting that curved nanofiber substrates are more suitable for promoting differentiation of salivary gland cells.

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Formation of post-confluence structure in human parotid gland acinar cells on PLGA through regulation of E-cadherin

Cited by 16 publications

References 29 publications

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

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

Biomaterials-based strategies for salivary gland tissue regeneration

Salivary gland cell differentiation and organization on micropatterned PLGA nanofiber craters

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