Effects of Cell‐Based Therapy for Treating Tympanic Membrane Perforations in Mice. (15th March 2016)

• Record Type: Journal Article
• Authors: Goncalves, Stefania; Bas, Esperanza; Goldstein, Bradley J.; Angeli, Simon
• Is Part Of: Otolaryngology--head and neck surgery. Volume 154:Number 6(2016:Jun.)
• Page Start: 1106
• Page End: 1114
• Publication Date: 2016-03-15
• Subjects: tympanic membrane perforations -- stem cells -- bone marrow–derived stem cells -- differentiation -- wound healing -- alternative therapy -- hyaluronate‐based biomaterials -- porcine‐derived collagen scaffold; Head -- Surgery -- Periodicals; Neck -- Surgery -- Periodicals; Otolaryngology -- Periodicals; 617.51
• DOI: 10.1177/0194599816636845
• Languages: English
• ISSNs: 0194-5998

Abstract

Abstract : Objective: To investigate the effectiveness of scaffold‐embedded mesenchymal stem cells (MSCs) as a topical treatment for healing tympanic membrane perforations (TMPs) in a mouse model. Study Design: Prospective animal study. Setting: Experimental. Subjects and Methods: In vitro: under sterile conditions, porcine‐derived (Gelita‐Spon [GS]), hyaluronate‐derived (EpiDisc [ED]), and polyvinyl alcohol (PVA) scaffolds were cut into small pieces and cocultured with murine bone marrow–derived MSCs (BM‐MSCs) expressing green fluorescent protein (GFP) for 72 hours. The cultures were either analyzed by confocal microscopy or used for subsequent in vivo experiments. In vivo: 26 mice were divided into 3 groups (ie, control [n = 9], GS [n = 8], ED [n = 9]). Under general anesthesia, TMPs of equal sizes were performed bilaterally using a sterile 27‐gauge needle under a surgical microscope. The BM‐MSCs embedded within GS or ED scaffolds were soaked in phosphate‐buffered saline and then topically applied on right TMPs, and scaffolds alone were applied on left TMPs 6 to 8 hours after injury. Control mice did not receive treatment. On day 7, animals were euthanized and bullae were harvested for histological analysis. Results: In vitro: BM‐MSCs grew well on both GS ( P = . 0012) and ED ( P = . 0001) scaffolds compared with PVA. In vivo: 100% of untreated (control) TMPs remained open after 7 days. Animals treated with MSC‐embedded ED scaffolds had a higher percentage of TMP closure ( P = . 016) and a thicker neotympanum ( P = . 0033) than control animals. The experimentally applied BM‐MSCs engrafted and differentiated into epithelial cells suggested by the colocalized expression of cytokeratin‐19 and GFP. Conclusions: The topical application of bone marrow–derived MSCs enhances the healing of TMPs in this animal model and is a promising alternative to tympanoplasty.