A Gingiva-Derived Mesenchymal Stem Cell-Laden Porcine Small Intestinal Submucosa Extracellular Matrix Construct Promotes Myomucosal Regeneration of the Tongue

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Departmental Papers (Dental)
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combinatorial construct
fibrosis
gingiva-derived MSCs
SIS-ECM
skeletal muscle progenitors
tongue regeneration
wound healing
Animals
Blotting
Western
Cells
Cultured
Extracellular Matrix
Female
Gingiva
Humans
Intestine
Small
Mesenchymal Stromal Cells
Rats
Rats
Sprague-Dawley
Swine
Tissue Engineering
Tissue Scaffolds
Tongue
Cell culture
Cells
Cytology
Defects
Muscle
Stem cells
collagen type 1
MyoD protein
myogenic factor 5
transcription factor PAX7
combinatorial construct
fibrosis
gingiva-derived MSCs
Skeletal muscle
tongue regeneration
Wound healing
animal experiment
Article
body weight
controlled study
epithelization
extracellular matrix
female
fluorescence microscopy
gingiva
human
human tissue
immunofluorescence
in vitro study
intestine mucosa
mesenchymal stem cell
muscle regeneration
nonhuman
normal human
priority journal
protein expression
rat
tissue regeneration
tongue
wound healing
animal
cell culture
cytology
extracellular matrix
gingiva
mesenchymal stroma cell
metabolism
pig
procedures
small intestine
Sprague Dawley rat
tissue engineering
tissue scaffold
Western blotting
Tissue
Dentistry
Oral and Maxillofacial Surgery
Oral Biology and Oral Pathology
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Xu, Qilin
Shanti, Rabie M
Zhang, Qunshou
Cannady, Steven B
O'Malley, Bert W
Chen, C D
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Abstract

In the oral cavity, the tongue is the anatomic subsite most commonly involved by invasive squamous cell carcinoma. Current treatment protocols often require significant tissue resection to achieve adequate negative margins and optimal local tumor control. Reconstruction of the tongue while preserving and/or restoring its critical vocal, chewing, and swallowing functions remains one of the major challenges in head and neck oncologic surgery. We investigated the in vitro feasibility of fabricating a novel combinatorial construct using porcine small intestinal submucosa extracellular matrix (SIS-ECM) and human gingiva-derived mesenchymal stem cells (GMSCs) as a GMSC/SIS-ECM tissue graft for the tongue reconstruction. We developed a rat model of critical-sized myomucosal defect of the tongue that allowed the testing of therapeutic effects of an acellular SIS-ECM construct versus a GMSC/SIS-ECM construct on repair and regeneration of the tongue defect. We showed that the GMSC/SIS-ECM construct engrafted at the host recipient site, promoted soft tissue healing, and regenerated the muscular layer, compared to the SIS-ECM alone or nontreated defect controls. Furthermore, our results revealed that transplantation of the GMSC/SIS-ECM construct significantly increased the expression of several myogenic transcriptional factors and simultaneously suppressed the expression of type I collagen at the wounded area of the tongue. These compelling findings suggest that, unlike the tongue contracture and fibrosis of the nontreated defect group, transplantation of the combinatorial GMSC/SIS-ECM constructs accelerates wound healing and muscle regeneration and maintains the overall tongue shape, possibly by both enhancing the function of endogenous skeletal progenitor cells and suppressing fibrosis. Together, our findings indicate that GMSC/SIS-ECM potentially served as a myomucosal graft for tongue reconstruction postsurgery of head and neck cancer. © Copyright 2017, Mary Ann Liebert, Inc.

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2017-04-01
Journal title
Tissue Engineering - Part A.
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