Nasal Mucosal Cell Research Articles

The impact of hydroxybutyl chitosan and 5-fluorouracil on the procedure of endoscopic endonasal dacryocystorhinostomy.

To investigate the effects of hydroxybutyl chitosan (HBCS) with and without 5-fluorouracil (5-FU) during endoscopic endonasal dacryocystorhinostomy (Endo-DCR). In addition, the present study observed the impact of HBCS and 5-FU on the functions of the nasal mucosal cell population in vivo. Patients were randomized into HBCS (group A), HBCS combined with 5-FU (group B), and gelatin sponge control group (group C). 16S rRNA high-throughput sequencing technology examined the conjunctival sac and nasal flora changes. In addition, CCK8, cell scratching, and flow cytometry were used to investigate the effects of HBCS and 5-FU on the nasal mucosal cell populations. Subjects in groups A, B, and C had anastomotic areas of 21.83 ± 12.69 mm2, 21.57 ± 14.53 mm2, and 12.45 ± 8.16 mm2, respectively (P = 0.0359). Group A had less severe epiphora than the other two groups at 1-, 2-, and 12-week postoperative follow-up (P < 0.05). Complications around the anastomosis in group A were the least severe of the three groups (P = 0.0259). After surgery, the proportion of pathogenic bacteria in the conjunctival sac and nasal cavity was higher in groups A and B than in healthy adults. At the 2-week follow-up, the structure of nasal flora in group A was more similar to that of the healthy adults compared to group B. Intraoperative use of HBCS at the anastomose improves the postoperative outcome of En-DCR. 5-FU cannot give better postoperative results in En-DCR and is detrimental to the normalization of the postoperative flora in patients with chronic dacryocystitis. At the cellular level, both HBCS and 5-FU inhibit the migration of nasal mucosal cell populations, and 5-FU inhibits proliferation but does not promote apoptosis.

The Cultivation Modality and Barrier Maturity Modulate the Toxicity of Industrial Zinc Oxide and Titanium Dioxide Nanoparticles on Nasal, Buccal, Bronchial, and Alveolar Mucosa Cell-Derived Barrier Models.

As common industrial by-products, airborne engineered nanomaterials are considered important environmental toxins to monitor due to their potential health risks to humans and animals. The main uptake routes of airborne nanoparticles are nasal and/or oral inhalation, which are known to enable the transfer of nanomaterials into the bloodstream resulting in the rapid distribution throughout the human body. Consequently, mucosal barriers present in the nose, buccal, and lung have been identified and intensively studied as the key tissue barrier to nanoparticle translocation. Despite decades of research, surprisingly little is known about the differences among various mucosa tissue types to tolerate nanoparticle exposures. One limitation in comparing nanotoxicological data sets can be linked to a lack of harmonization and standardization of cell-based assays, where (a) different cultivation conditions such as an air-liquid interface or submerged cultures, (b) varying barrier maturity, and (c) diverse media substitutes have been used. The current comparative nanotoxicological study, therefore, aims at analyzing the toxic effects of nanomaterials on four human mucosa barrier models including nasal (RPMI2650), buccal (TR146), alveolar (A549), and bronchial (Calu-3) mucosal cell lines to better understand the modulating effects of tissue maturity, cultivation conditions, and tissue type using standard transwell cultivations at liquid-liquid and air-liquid interfaces. Overall, cell size, confluency, tight junction localization, and cell viability as well as barrier formation using 50% and 100% confluency was monitored using trans-epithelial-electrical resistance (TEER) measurements and resazurin-based Presto Blue assays of immature (e.g., 5 days) and mature (e.g., 22 days) cultures in the presence and absence of corticosteroids such as hydrocortisone. Results of our study show that cellular viability in response to increasing nanoparticle exposure scenarios is highly compound and cell-type specific (TR146 6 ± 0.7% at 2 mM ZnO (ZnO) vs. ~90% at 2 mM TiO2 (TiO2) for 24 h; Calu3 93.9 ± 4.21% at 2 mM ZnO vs. ~100% at 2 mM TiO2). Nanoparticle-induced cytotoxic effects under air-liquid cultivation conditions declined in RPMI2650, A549, TR146, and Calu-3 cells (~0.7 to ~0.2-fold), with increasing 50 to 100% barrier maturity under the influence of ZnO (2 mM). Cell viability in early and late mucosa barriers where hardly influenced by TiO2 as well as most cell types did not fall below 77% viability when added to Individual ALI cultures. Fully maturated bronchial mucosal cell barrier models cultivated under ALI conditions showed less tolerance to acute ZnO nanoparticle exposures (~50% remaining viability at 2 mM ZnO for 24 h) than the similarly treated but more robust nasal (~74%), buccal (~73%), and alveolar (~82%) cell-based models.

PRMT1 inhibits apoptosis of nasopharyngeal carcinoma cells by promoting RRM2 expression

To verify whether PRMT1 inhibits apoptosis of nasopharyngeal carcinoma (NPC) cells by promoting RRM2 expression. Immunohistochemistry and Western blotting were performed to detect the relative expression of PRMT1 and RRM2 in NPC and adjacent tissues and in different NPC cell lines and a normal nasal mucosal epithelial cell line (HNEpC). Experiments of PRMT1 or RRM2 overexpression or siRNA-mediated PRMT1 or RRM2 knockdown were carried out in CNE-2 cells to investigate the relationship between PRMT1 and RRM2 expressions using Western blotting. Apoptosis of the transfected cells was detected using Annexin V-FITC/PI apoptosis detection kit, and the production of intracellular reactive oxygen species (ROS) was determined using a ROS detection kit. Compared with adjacent tissues and HNEpC cells, NPC tissues and cell lines expressed significantly higher levels of PRMT1 and RRM2 (P < 0.05). In CNE-2 cells with PRMT1 or RRM2 overexpression or knockdown, Western blotting demonstrated that PRMT1 could positively regulate the expression of RRM2 (P < 0.05). Overexpression of PRMT1 or RRM2 significantly reduced intracellular ROS production and apoptosis rate of CNE-2 cells (P < 0.05), and PRMT1 or RRM2 knockdown strongly increased ROS production and cell apoptosis (P < 0.05). Overexpression of either PRMT1 or RRM2 significantly decreased the expressions of cleaved caspase-3 and cleaved caspase-8 proteins (P < 0.05), and PRMT1 or RRM2 knockdown obviously promoted their expressions (P < 0.05). PRMT1 knockdown combined with RRM2 overexpression, as compared with PRMT1 knockdown only, significantly decreased ROS production and cell apoptosis (P < 0.05) as well as the protein expressions of cleaved caspase-3 and cleaved caspase-8 in CNE-2 cells (P < 0.05). The high expression of PRMT1 in NPC inhibits apoptosis of NPC cells by promoting the expression of RRM2.

Cell sheet transplantation prevents inflammatory adhesions: A new treatment for adhesive otitis media.

IntroductionWe developed a new treatment method that combines tympanoplasty with transplantation of autologous cultured nasal mucosal epithelial cell sheets to regenerate the mucosa of patients with adhesive otitis media, which has been difficult to treat effectively. We verified whether this procedure could be performed safely and measured its therapeutic efficacy.MethodsAutologous nasal mucosal epithelial cell sheets were manufactured at a good manufacturing practice-compliant cell processing facility using autologous nasal mucosal tissue. We performed tympanoplasty and transplanted the cell sheets into the middle ear cavity in six patients with adhesive otitis media.ResultsThe manufactured autologous cultured epithelial cell sheets met the predetermined quality standards and were successfully transplanted safely in all cases. Computed tomography findings after cell sheet transplantation showed that aeration in the tympanic cavity was maintained or restored in five of the six patients (83.3%). Four of the six (66.7%) patients had postoperative air-bone gap within 20 dB, which is considered a postoperative success in tympanoplasty for chronic middle ear disease.ConclusionsThe results of this clinical study suggest that tympanoplasty with cell sheet transplantation can be used to treat adhesive otitis media by reliably preventing re-adhesion of the tympanic membrane.

Temporary Storage of the Human Nasal Tissue and Cell Sheet for Wound Repair.

Temporary storage of nasal tissues and nasal cell sheets, which entails transportation between hospitals and cell culture facilities, is an important issue in regenerative medicine. Herein, we investigated the preservation of chilled and frozen nasal tissues and expiry dates of ready-to-use nasal cell sheets. Although the cell number in preserved tissues was lower than that in fresh tissue, nasal cell sheets could be fabricated from tissues that had been refrigerated for 5 days and frozen–thawed over 5 days. Moreover, the nasal mucosal cell sheets were preserved in a non-hazardous buffer. The cell number, viability, and structure were not maintained in saline containing E-cadherin for 2 days; however, these were maintained in Hank’s balanced salt solution for 2 days, but not for 5 days. To assess the proliferation capacity of cells in the stored cell sheets, we performed cell sheet grafting assays in vitro. Cell sheets stored in Hank’s balanced salt solution for 2 days adhered to collagen gel and expanded normally. Our results show that nasal tissues can be stored temporarily in refrigerators or deep freezers, and Hank’s balanced salt solution can be used for preservation of ready-to-use cell sheets for a few days.

A novel self-assembled epitope peptide nanoemulsion vaccine targeting nasal mucosal epithelial cell for reinvigorating CD8+ T cell immune activity and inhibiting tumor progression

Epitope peptides are not suitable for nasal administration immunity due to their poor immunogenicity and low delivery efficiency. Here, we reported an intranasal self-assembled nanovaccine (I-OVA NE), which was loaded with the peptides IKVAV-OVA257–264 (I-OVA), a laminin peptide (Ile-Lys-Val-ala-Val, IKVAV) and OVA257–264 epitope conjugated peptide. This nanovaccine with I-OVA at a concentration of 4 mg/mL showed the average particle size of 30.37 ± 2.49 nm, zeta potential of −16.67 ± 1.76 mV, and encapsulation rate of 84.07 ± 7.59%. Moreover, the mucin did not alter its stability (size, PdI and zeta potential). And it also had no obvious acute pathological changes neither in the nasal mucosa nor lung tissues after nasal administration. Meanwhile, the antigen uptake of I-OVA NE was promoted, and the nasal residence time was also prolonged in vivo. Besides, the uptake rate of this nanovaccine was obviously higher than that of free I-OVA (P < 0.001) after blocking by the integrin antibody, suggesting that the binding of IKVAV to integrin is involved in the epitope peptide uptake. Importantly, this nanovaccine enhanced peptide-specific CD8+T cells exhibiting OVA257–264-specific CTL activity and Th1 immune response, leading to the induction of the protective immunity in E.G7-OVA tumor-bearing mice. Overall, these data indicate that I-OVA NE can be an applicable strategy of tumor vaccine development.

Preclinical assessment of transplantable human nasal mucosal epithelial cell sheets.

IntroductionWe previously reported a new cell transplantation therapy for patients with intractable otitis media using autologous nasal mucosal epithelial cell sheets, manufactured using temperature-responsive cell culture inserts. The current study aimed to verify whether the transplantable cell sheets could be manufactured for application in clinical trials, according to standard operational procedures (SOP), in a cell processing facility (CPF).MethodsHuman nasal mucosal epithelial cells from four volunteer donors were aseptically cultured and transplantable cell sheets successfully manufactured, with reproducibility, using temperature-responsive cell culture inserts in the CPF. During the manufacture of cell sheets, the CPF environment was confirmed to be aseptic by sterilization tests. Purity of the cell sheets was confirmed by histological analysis and flow cytometry. Both safety and quality of the human nasal mucosal epithelial cell sheets were validated.ResultsThe cultured and manipulated human nasal mucosal epithelial cells showed no evidence of malignant transformation in vitro. The study confirmed the safety and suitability of the manufactured human nasal mucosal epithelial cell sheets for use in clinical trials.ConclusionsThe results led to the establishment of a coherent system in which transplantation could be achieved smoothly.

On the in vivo origin of human nasal mesenchymal stem cell cultures.

ObjectivesMesenchymal stem cells (MSCs), classically expanded in culture from bone marrow, are of broad interest to the regenerative medicine community. Human nasal turbinate mesenchymal‐like stem cell cultures have also been described, defined by an in vitro phenotype similar to bone marrow MSCs. Nonetheless, the identity in vivo of the cells that give rise to nasal MSC‐like cultures remains unclear, and these cells are often suggested to be related to olfactory lineages. Here, we sought to define the in vivo phenotype of human nasal MSC‐like cells.MethodsHuman turbinate tissue samples were used for RNA and immunohistochemical analysis. We also analyzed a recently published single cell RNA‐sequencing dataset from adult human olfactory and respiratory mucosa samples from our lab, to focus on cell populations expressing MSC markers. Immunochemistry was performed to stain turbinate sections and nasal MSC cultures for selected markers.ResultsWhile there is no single MSC‐specific gene, we identified a human nasal mucosal cell population in vivo that uniquely expressed transcripts characteristic of typical MSC cultures, including ENG (CD105), NES, and CD34, and lacked expression of other transcripts associated with surface epithelia. The expression of transcription factors such as SOX17, EBF1, and FOXP1 suggests cells in the MSC‐like cluster maintain an ability to direct cell fate, consistent with the behavior of nasal MSC‐like cells in vitro. SOX17 was found to be uniformly expressed by nasal MSC cultures, consistent with the in vivo data. Immunohistochemistry of human nasal tissue samples indicated that ENG, CD34, and SOX17 expression localized selectively to cells surrounding blood vessels in the lamina propria.ConclusionOur findings provide evidence that the in vivo origin of nasal MSC‐like cultures is likely a vascular or pericyte population, rather than cells related to the olfactory neuronal lineage.Level of evidenceNA.

ROCK inhibitor combined with Ca2+ controls the myosin II activation and optimizes human nasal epithelial cell sheets

The proliferation and differentiation of cultured epithelial cells may be modified by Rho-associated kinase (ROCK) inhibition and extracellular Ca2+ concentration. However, it was not known whether a combination would influence the behavior of cultured epithelial cells through changes in the phosphorylation of non-muscle myosin light chain II (MLC). Here we show that the combination of ROCK inhibition with Ca2+ elevation regulated the phosphorylation of MLC and improved both cell expansion and cell–cell adhesion during the culture of human nasal mucosal epithelial cell sheets. During explant culture, Ca2+ enhanced the adhesion of nasal mucosal tissue, while ROCK inhibition downregulated MLC phosphorylation and promoted cell proliferation. During cell sheet culture, an elevation of extracellular Ca2+ promoted MLC phosphorylation and formation of cell–cell junctions, allowing the harvesting of cell sheets without collapse. Moreover, an in vitro grafting assay revealed that ROCK inhibition increased the expansion of cell sheets three-fold (an effect maintained when Ca2+ was also elevated), implying better wound healing potential. We suggest that combining ROCK inhibition with elevation of Ca2+ could facilitate the fabrication of many types of cell graft.

Lessons learned from conventional animals: Encouragement to use specific-pathogen-free animals.

Experimental rabbits provide evidence for translational research regarding the pathogenies or treatment of human diseases. We developed a novel method for regenerating the middle ear mucosa using autologous cultured nasal mucosal epithelial cell sheets, and evaluated the wound healing process in the middle ear mucosa of experimental rabbits. Nonetheless, vigilant microbiological monitoring of experimental animals is essential to effectively prevent a decline in their health conditions, which may affect the research results. We experimented with contamination of Pasteurella multocida in non-specific-pathogen-free (SPF) rabbits (without microbiological monitoring). Most non-SPF rabbits had otitis media, whereas SPF rabbits did not, which affected their results during the mucosal regeneration study. The contamination was resolved by changing the experimental design from using non-SPF rabbits to that using SPF rabbits. It is crucial to use the SPF animals for any surgical intervention studies.

Internalization Mechanism of Phenylboronic-Acid-Decorated Nanoplatform for Enhanced Nasal Insulin Delivery

Insulin injection causes great pain to the patient, and nasal mucosal administration of insulin is a novel route for the treatment of diabetes. This strategy could protect insulin from either extensive first-pass metabolism or enzyme degradation in the gastrointestinal tract. With the dynamic boronate esters reversibly formed by phenylboronic acid and diols on nasal mucosal epithelial cell surfaces, we herein developed phenylboronic-acid-functionalized dextran nanoplatforms to enhance the permeability of cargos and boost penetration. The nanoplatforms with excellent loading capacity exhibited significant endocytosis compared with naked insulin. The mechanism of endocytosis was involved in clathrin- and lipid raft/caveolae-dependent endocytic pathways. The in vivo nasal delivery of insulin suggested that these nanoplatforms did not trigger nasal epithelial inflammation and greatly decreased blood sugar levels and improved insulin bioavailability. Collectively, this proof-of-concept study demonstrates a novel carrier of phenylboronic-acid-decorated polymer for insulin delivery and provides a promising approach for the development of a diabetes therapeutic strategy.

RORA Overexpression Alleviates Nasal Mucosal Injury and Enhances Red Blood Cell Immune Adhesion Function in a Mouse Model of Allergic Rhinitis via Inactivation of the Wnt/β-Catenin Signaling Pathway

Background: In this study, we examined whether RORA (retinoic acid receptor-related orphan receptor alpha) was capable of alleviating the progression of allergic rhinitis (AR). Methods: In order to elucidate the possible effects of RORA and the regulatory mechanism between RORA and the Wnt/β-catenin signaling pathway, mouse AR models were established and treated with RORA vector, siRNA against RORA, or the Wnt/β-catenin pathway inhibitor WIF-1. Subsequently, the serum levels of inflammatory cytokines (IgE, INF-γ, IL-1β, IL-4, and IL-17), red blood cell (RBC) immune adhesion function, the levels of RORA, β-catenin, and GSK3β, as well as the extent of β-catenin and GSK-3β phosphorylation were evaluated and measured. Results: The OVA-induced AR mouse model exhibited obvious nasal mucosal injury and inflammatory cell infiltration. RORA overexpression or the inactivation of the Wnt/β-catenin signaling pathway was uncovered as a way to ameliorate nasal mucosal injury and eosinophil infiltration of the OVA-induced AR mouse model. On the other hand, it reduced the number of eosinophils and mast cells, which also resulted in downregulated expression of IgE, INF-γ, IL-1β, IL-4, IL-17, β-catenin, and GSK-3β. Moreover, this led to a decreased extent of β-catenin and GSK-3β phosphorylation, while the rates of C₃b receptor rosette and Ic rosette were elevated. Conclusion: Taken together, the key findings provided evidence suggesting that the elevated RORA could potentially alleviate nasal mucosal injury and simultaneously enhance RBC immune adhesion function through the inhibition of the Wnt/β-catenin signaling pathway activation in an OVA-induced AR mouse model. This emphasizes a novel therapeutic target for the treatment of AR.

Analysis of human nasal mucosal cell sheets fabricated using transported tissue and blood specimens.

Previously, we succeeded in transplanting autologous nasal mucosal cell sheets in the middle ears of 5 patients, who underwent cholesteatoma resection, which prevents recurrence of cholesteatoma in clinical settings. Current good manufacturing practice (GMP) standards for human cell cultivation requires the establishment of cell processing centers (CPC) which act as germ-free facilities. However, due to practical difficulties involved in establishing and maintaining such facilities at each individual hospital, a functional transport system is felt to be needed for the continuation of effective regenerative therapy. In the current study, nasal mucosal tissue and autologous blood obtained from 3 human volunteers were transported for over 3 h. Disinfected nasal tissues were cultured using keratinocyte culture medium, which included autologous serum prepared from blood. After 24 d, cultured nasal mucosal cells were transported for over 3 h and subsequently assessed for cell number, viability and purity. Moreover, CK4, CK8, and CK18 were analyzed the suitability of these nasal mucosal cell sheets for middle ear regenerative therapy.Overall, we confirmed that nasal mucosal cell sheets can be fabricated using transported nasal mucosal tissue and blood. This study would be contribute to establish a new regenerative therapy for clinical application, accompanied with transportation between companies and hospitals.

UPA affects the CRSsNP nasal mucosa epithelium apoptosis by regulating WIF1

Chronic rhinosinusitis without nasal polyps (CRSsNP) is the main type of Chronic rhinosinusitis (CRS) and is a common otorhinolaryngologic disease worldwide. However, the mechanisms of CRSsNP remain poorly understood. In this study, C57BL/6J wild-type and urokinase-type plasminogen activator (uPA) gene knockout (uPA-/-) mice were used to construct the CRSsNP model. Primary human nasal epithelial cells (HNEC) were isolated from CRSsNP patient and treated with uPA knockdown/overexpression lentivirus. CCK-8 and Annexin-V/PI staining were used to detected cell proliferation and apoptosis. In vivo, we found that uPA depletion alleviated mucosal inflammation in the CRSsNP mice model. Wnt inhibitory factor 1 (WIF1) was upregulated in the uPA-/- CRSsNP mice model. In vitro, inhibition of uPA increased cell proliferation and decreased cell apoptosis. Mechanistically, uPA depletion upregulated WIF1 and BCL2 expression, and reduced the expression level of BAX in CRSsNP HNEC. In contrast, decreased cell proliferation and increased cell apoptosis were observed after uPA overexpression. Consistently, a reduction in WIF1 and BCL2 expression levels and an increase in the BAX expression level were observed upon uPA ectopic expression. Furthermore, WIF1 overexpression rescued the effects caused by uPA overexpression in vitro. In conclusion, uPA affects the CRSsNP nasal mucosal epithelium cell apoptosis by upregulating WIF1. To our knowledge, this is the first study to explore the role of uPA in CRSsNP to date.

Evaluation of antifibrotic effect of pirfenidone on human nasal mucosal fibroblast cell culture

Background: One of the main reasons of failure in surgical treatment of primary acquired nasolacrimal duct obstruction is excessive postoperative scarring of the dacryostomy. Despite the variety of procedures designed to prevent this, conflicting evidence of their efficacy and safety provide incentive for further research of antifibrotic therapeutics for adjunctive use in dacryocystorhinostomy.Aims: To evaluate the antifibrotic effect of pirfenidone on human nasal mucosal fibroblast cell culture.Materials and methods: Human nasal mucosal fibroblast cell cultures were established using samples obtained from 3 consecutive patients undergoing endonasal endoscopic dacryocystorhinostomy. Cell viability following treatment with pirfenidone was evaluated using MTS-assay. Induced inhibition of cell proliferation and migration was determined using scratch wound assay.Results: In this study pirfenidone exhibited a significant dose-dependent inhibiting effect on fibroblast proliferation with insignificant cell toxicity. Cell viability following 48 hours of incubation with various pirfenidone concentrations did not drop below 80%. The recovery of the fibroblast monolayer assessed after 24 hours of incubation was 84.88 and 8.26% in the control group, at a drug concentration of 0.15 mg/ml. Cell proliferation and migration was severely inhibited in cell culture specimens treated with pirfenidone compared to controls. The difference between groups was statistically significant (p=0,001).Conclusions: In our study pirfenidone demonstrated a pronounced antifibrotic effect. It is unlikely that inhibition of proliferation and migration of human nasal mucosal fibroblasts is mediated by cell toxicity of this medication as it was evaluated as low. Nonetheless an in vitro analysis is insufficient to judge pirfenidone’s efficacy and safety in preventing cicatrix formation following dacrycystorhinostomy.

Realization of middle ear mucosal regeneration by cultured nasal mucosal epithelial cell sheet transplantation

Realization of middle ear mucosal regeneration by cultured nasal mucosal epithelial cell sheet transplantation

Middle ear mucosal regeneration by tissue-engineered cell sheet transplantation

The recurrence of cholesteatoma after surgical treatment often occurs as a result of poor mucosal regeneration in the middle ear cavity and mastoid cavity and changes, such as granulation tissue formation, which impair gas exchange in the middle ear cavity. Conventional tympanoplasty often results in a lack of mucosal regeneration in the resected area of the mastoid cavity. In particular, mucosal regeneration in a poorly pneumatized mastoid cavity is extremely difficult. If the middle ear mucosa can be preserved or rapid postoperative regeneration of mucosa on the exposed bone surface can be achieved after middle ear surgery, the results of surgical treatment for otitis media, including cholesteatoma, can potentially be improved and the physiological function of the middle ear can be recovered. To overcome these limitations, we developed a novel treatment method combining tympanoplasty and autologous nasal mucosal epithelial cell sheet transplantation for postoperative regeneration of the middle ear mucosa. In clinical research, we endoscopically removed an approximately 10 × 10 mm2 piece of nasal mucosal tissue. Tissue-engineered autologous nasal mucosal epithelial cell sheets were fabricated by culturing the harvested cells in an aseptic environment in a good manufacturing practice-compliant cell processing facility. The cultivated cell sheets were transplanted, during tympanoplasty, onto the exposed bony surface of the attic of the tympanic and mastoid cavities where the mucosa had been lost. We performed this procedure on four patients with middle ear cholesteatoma and one patient with adhesive otitis media. All patients showed favorable postoperative course with no adverse events or complications and the patients’ hearing ability post-transplantation remained good.

Middle ear mucosal regeneration by nasal mucosal epithelial cell sheets transplantation

middle ear mucosal regeneration by nasal mucosal epithelial cell sheets transplantation

N775 (Basic Research on the Otological Fields), Middle Ear Mucosal Regeneration by Nasal Mucosal Epithelial Cell Sheets Transplantation

N775 (Basic Research on the Otological Fields), Middle Ear Mucosal Regeneration by Nasal Mucosal Epithelial Cell Sheets Transplantation

The effect of transplantation of nasal mucosal epithelial cell sheets after middle ear surgery in a rabbit model

Postoperative regeneration of the middle ear mucosa and pneumatization of the middle ear cavity are of great importance after middle ear surgery. This study developed a new method to transplant autologous nasal mucosal epithelial cell sheets into the damaged middle ear cavity. The aim of this study was to evaluate postoperative healing after the transplantation of the cell sheets. Rabbit nasal mucosal epithelial cell sheets were fabricated on a temperature-responsive culture dish, and transplanted into the damaged middle ear of rabbit, which was surgically created. The healing of middle ears was evaluated by histology and X-ray computed tomography after transplantation. Functional evaluation was performed by measuring the maximum middle ear total pressure reflecting a trans-mucosal gas exchange function. Two control groups were used: the normal control group and the mucosa-eliminated control group. Transplantation of cell sheets suppressed the bone hyperplasia and the narrowing of pneumatic space in the middle ear cavity compared with the mucosa-eliminated control group. The mucosal gas exchange function was also better in the cell sheet-transplanted group. Nasal mucosal epithelial cell sheet was confirmed to be useful as an effective graft material after middle ear surgery and hopefully become a novel therapy in the future.