Searching for a rat model of chronic tympanic membrane perforation: Healing delayed by mitomycin C/dexamethasone but not paper implantation or iterative myringotomy

Wang, Allen Y.; Shen, Yi; Liew, Lawrence J.; Wang, Jeffrey T.; Unge, Magnus von; Atlas, Marcus D.; Dilley, Rodney J.

doi:10.1016/j.ijporl.2015.05.020

Cited by 19 publications

(19 citation statements)

References 38 publications

(59 reference statements)

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“…The current clinical and scientific literature defines chronic perforations as lasting more than 2-3 months. [3][4][5][6][7][8] In a previous letter, this author also agrees with this definition and states that most authors consider a patient for surgery after a perforation has been present for 3 months. In this letter, the author then references his own work for a treatment in chronic perforations, yet the actual study describes recruitment of perforations present for 1 month (subacute perforations) and not chronic perforations.…”

mentioning

confidence: 53%

In Response to the Letter to the Editor Regarding: Heparin Binding–Epidermal Growth Factor-Like Growth Factor for the Regeneration of Chronic Tympanic Membrane Perforations in Mice

Luke

KimSungwoo

Kursad

et al. 2016

Tissue Engineering Part A

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mentioning

confidence: 53%

In Response to the Letter to the Editor Regarding: Heparin Binding–Epidermal Growth Factor-Like Growth Factor for the Regeneration of Chronic Tympanic Membrane Perforations in Mice

Luke

KimSungwoo

Kursad

et al. 2016

Tissue Engineering Part A

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“…Moreover, this model has the potential for ex vivo testing of novel graft materials for tympanoplasty. In vivo studies from our group have previously investigated re-myringotomy as a method to delay TMP healing in rats.We found that instead re-myringotomy accelerated TMP closure and was associated with epidermal proliferation [25]. It is known that physical trauma activates cell proliferative mechanisms in vivo, and we proposed that this can be used to increase yield in our ex vivo explant culture.…”

Section: Discussionmentioning

confidence: 81%

Tympanic Membrane Derived Stem Cell-Like Cultures for Tissue Regeneration

Liew

Chen

Wang

et al. 2018

Stem Cells and Development

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Epidermal cells with stem cell-like characteristics have been identified in the tympanic membrane (TM) and localized specifically to the umbo and annulus regions. While they have been proposed to play a role in the regeneration of both acute and chronic TM perforations, evidence for the mechanism and regulation of their contribution is not yet described. Indeed, the behavior of these putative stem cells is largely unknown, in part due to a lack of refined methods for efficient cell isolation. In this study, we compared different explant techniques using normal and perforated rat TM tissues and investigated their ex vivo characteristics. TM after perforation in vivo showed increased staining for epidermal stem cell markers integrin β1 and cytokeratin (CK) 19, and for proliferation Ki-67, indicating activation of the proliferative centers. A mixed population of fibroblasts and epithelial cells were isolated from explant cultures. Excised TM umbo implanted on a culture well insert was the most effective technique. Explants made from perforated TM produced cells before those from unperforated TM. More importantly, the implanted TM umbo organoid was capable of producing cells in a continuous manner, allowing subsequent harvest using trypsin. Primary rat TM epithelial cell cultures positive for pancytokeratin had colony forming activity and could be enriched for CK 19-positive cells that were capable of culture expansion by proliferation and cell migration when subject to a wound assay. Taken together, trauma to the TM activated the proliferative centers and prompted early cell production from TM umbo organoid cultures, which produced TM stem cell-like cultures that proved suitable for tissue engineering of the TM.

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“…Topical applications of mitomycin C and dexamethasone (M/D) have been shown by another group [11,19] in creating chronic TM perforations in a rat model. However, our research group recently found that topical M/D delayed healing but not enough to produce a chronic TMP in rats [26].…”

Section: Introductionmentioning

confidence: 93%

“…mitomycin C [11,19], steroids [10,20]) and by genetic modification [13]. Controversies and discussions have been generated regarding both the reproducibility and validity of previously reported methods [21][22][23][24][25][26]. Topical applications of mitomycin C and dexamethasone (M/D) have been shown by another group [11,19] in creating chronic TM perforations in a rat model.…”

Section: Introductionmentioning

confidence: 99%

Rat model of chronic tympanic membrane perforation: A longitudinal histological evaluation of underlying mechanisms

Wang

Liew

Shen

et al. 2017

International Journal of Pediatric Otorhinolaryngology

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Searching for a rat model of chronic tympanic membrane perforation: Healing delayed by mitomycin C/dexamethasone but not paper implantation or iterative myringotomy

Cited by 19 publications

References 38 publications

In Response to the Letter to the Editor Regarding: Heparin Binding–Epidermal Growth Factor-Like Growth Factor for the Regeneration of Chronic Tympanic Membrane Perforations in Mice

In Response to the Letter to the Editor Regarding: Heparin Binding–Epidermal Growth Factor-Like Growth Factor for the Regeneration of Chronic Tympanic Membrane Perforations in Mice

Tympanic Membrane Derived Stem Cell-Like Cultures for Tissue Regeneration

Rat model of chronic tympanic membrane perforation: A longitudinal histological evaluation of underlying mechanisms

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