Mesenchymal Stem Cells for Treatment of Delayed-Healing Tympanic Membrane Perforations Using Hyaluronate-based Laminas as a Delivery System: An Animal Model With Histopathologic Study

David Shahal, Stefania Goncalves, Simon I. Angeli

Research output: Contribution to journalArticlepeer-review

Abstract

Hypothesis:Bone marrow derived-mesenchymal stem cells (BM-MSCs) improve the healing of chronic tympanic membrane perforations (cTMPs) in an animal model.Background:cTMPs generate significant morbidity and reduced quality of life, usually requiring surgical assistance. With growing interest in alternative therapies, we sought to evaluate the effect of BM-MSC-therapy on the healing of cTMPs.Methods:Sixty cTMPs were established in C57Bl/6 mice and randomized into four groups: Hyaluronate scaffold as graft plus BM-MSCs (n-=-19 ears), scaffold plus cell culture media (n-=-16), scaffold plus phosphate-buffered saline (PBS, n-=-12), and no intervention (n-=-13). Hyaluronate scaffolds with or without BM-MSCs were applied on 8-week perforated eardrums. After a blinded assessment of perforation sizes at baseline and 2-weeks after treatment, mean perforation reduction rates (%) were compared. Histology characterization was then performed.Results:Mean perforation size reduction rates were significantly higher for cTMPs that received scaffolds plus BM-MSCs (Student's t test, p-=-0.0207, 12.3% [95% CI: 7.8-16.7]) and scaffolds plus cell culture media (p-=-0.0477, 11.3% [95% CI: 4.4-18.2]) when compared with no intervention (4.2% [95% CI: 1.2-7.2]). This was not observed when treating eardrums with scaffolds plus PBS (7.3% [95% CI: 2.7-11.9]). On histology, BM-MSC-treated eardrums demonstrated restoration of the trilaminar configuration and reduced inflammatory changes, while other groups developed tissue architecture disorganization and hypercellular infiltrates surrounding the perforation site.Conclusions:BM-MSCs and cell culture media equivalently increased cTMP healing rates. Cell-based therapy conferred a restoration of the trilaminar configuration of the eardrum with relatively compact and organized fibrous layers.

Original languageEnglish (US)
Pages (from-to)E497-E506
JournalOtology and Neurotology
Volume43
Issue number4
DOIs
StatePublished - Apr 1 2022
Externally publishedYes

Keywords

  • Bone marrow-derived mesenchymal stem cells
  • Hyaluronate-based biomaterials
  • Regenerative therapy
  • Stem cells
  • Tissue engineering
  • Tympanic membrane perforations
  • Wound healing

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Sensory Systems
  • Clinical Neurology

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