Departmental Papers (Dental)

Document Type

Journal Article

Date of this Version

4-2017

Publication Source

Tissue Engineering - Part A.

Volume

23

Issue

7-8

Start Page

301

Last Page

312

DOI

10.1089/ten.tea.2016.0342

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.

Keywords

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

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Date Posted: 10 February 2023

This document has been peer reviewed.