Enhanced tissue remodelling efficacy of adipose-derived mesenchymal stem cells using injectable matrices in radiation-damaged salivary gland model

J Tissue Eng Regen Med. 2018 Feb;12(2):e695-e706. doi: 10.1002/term.2352. Epub 2017 May 7.

Abstract

The present study was conducted to introduce the use of a delivery carrier for local transplantation of human adipose tissue-derived mesenchymal stem cells (AdMSCs) into the salivary gland (SG) and analyse its ability to enhance radioprotection of AdMSCs against irradiation (IR)-induced damage. An injectable porcine small intestinal submucosa (SIS) matrix was used as a cell delivery carrier, and human AdMSCs were contained within SIS hydrogel (AdMSC/SIS). After local injection into SGs of mice following local IR, morphological and functional changes were evaluated in the sham, vehicle [phosphate-buffered saline (PBS)], SIS, AdMSC and AdMSC/SIS groups. Local transplantation of AdMSC resulted in less fibrosis, regardless of the use of a carrier, but the AdMSC/SIS group showed more mucin-producing acini relative to those in the PBS group. Functional restoration of salivation capacity and salivary protein synthesis was achieved in AdMSC and AdMSC/SIS groups, with a greater tendency being observed in the AdMSC/SIS group. AdMSC treatment resulted in tissue remodelling with a greater number of salivary epithelial cells (AQP-5), SG progenitor cells (c-Kit), endothelial cells (CD31) and myoepithelial cells (α-SMA), among which endothelial and myoepithelial cells significantly increased in the AdMSC/SIS group relative to the AdMSC group. AdMSC treatment alleviated IR-induced cell death, and the anti-apoptotic and anti-oxidative effects of AdMSC were enhanced in the AdMSC/SIS group relative to the AdMSC group. These results suggest local transplantation of AdMSC improves tissue remodelling following radiation damage in SG tissue, and that use of a carrier enhances the protective effects of AdMSC-mediated cellular protection against IR via paracrine secretion. Copyright © 2016 John Wiley & Sons, Ltd.

Keywords: adipose tissue-derived mesenchymal stem cells; local transplantation; radiation; regeneration; salivary gland; small intestinal submucosa gel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / cytology*
  • Animals
  • Apoptosis / drug effects
  • Cell Survival / drug effects
  • Cytoprotection / drug effects
  • Female
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacology
  • Injections*
  • Intestinal Mucosa / drug effects
  • Mesenchymal Stem Cells / cytology*
  • Mesenchymal Stem Cells / drug effects
  • Mice
  • Models, Biological*
  • Reactive Oxygen Species / metabolism
  • Salivary Glands / drug effects
  • Salivary Glands / pathology*
  • Salivary Glands / physiopathology
  • Salivary Glands / radiation effects*
  • Swine

Substances

  • Reactive Oxygen Species
  • Hydrogel, Polyethylene Glycol Dimethacrylate