Document Detail

Implantable three-dimensional salivary spheroid assemblies demonstrate fluid and protein secretory responses to neurotransmitters.
MedLine Citation:
PMID:  23442148     Owner:  NLM     Status:  MEDLINE    
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, self-assembled into acini-like structures and expressed functional neurotransmitter receptors. Structures in 3D hydrogels merged to form organized 50 μm spheroids that could be maintained in culture for over 100 days and merged to form structures over 500 μm in size. Treatment of acini-like structures with the β-adrenergic agonists norepinephrine or isoproterenol increased granule production and α-amylase staining in treated structures, demonstrating regain of protein secretion. Upon treatment with the M3 muscarinic agonist acetylcholine, acini-like 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 acini-like 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.
Swati Pradhan-Bhatt; Daniel A Harrington; Randall L Duncan; Xinqiao Jia; Robert L Witt; Mary C Farach-Carson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-05-10
Journal Detail:
Title:  Tissue engineering. Part A     Volume:  19     ISSN:  1937-335X     ISO Abbreviation:  Tissue Eng Part A     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-05-29     Completed Date:  2014-01-03     Revised Date:  2014-07-01    
Medline Journal Info:
Nlm Unique ID:  101466659     Medline TA:  Tissue Eng Part A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1610-20     Citation Subset:  IM    
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MeSH Terms
Cells, Cultured
Fluorescent Antibody Technique
Hydrogel / chemistry
Isoproterenol / pharmacology
Neurotransmitter Agents / pharmacology*
Norepinephrine / pharmacology
Salivary Glands / cytology*,  drug effects,  metabolism*
Tissue Engineering / methods
Grant Support
Reg. No./Substance:
0/Neurotransmitter Agents; 25852-47-5/Hydrogel; L628TT009W/Isoproterenol; X4W3ENH1CV/Norepinephrine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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