Human Nasal Septum Research Articles

The Creation of an Average 3D Model of the Human Cartilaginous Nasal Septum and Its Biomimetic Applications.

The cartilaginous nasal septum is integral to the overall structure of the nose. Developing our an-atomic understanding of the septum will improve the planning and techniques of septal surgeries. While the basic dimensions of the septum have previously been described, the average shape in the sagittal plane has yet to be established. Furthermore, determining the average shape allows for the creation of a mean three-dimensional (3D) septum model. To better understand the average septal shape, we dissected septums from 40 fresh human cadavers. Thickness was measured across pre-defined points on each specimen. Image processing in Photoshop was used to superimpose lateral photographs of the septums to determine the average shape. The average shape was then combined with thickness data to develop a 3D model. This model may be utilized in finite elemental analyses, creating theoretical results about septal properties that are more translatable to real-world clinical practice. Our 3D septum also has numerous applications for 3D printing. Realistic models can be created for educational or surgical planning purposes. In the future, our model could also serve as the basis for 3D-printed scaffolds to aid in tissue regeneration to reconstruct septal defects. The model can be viewed at the NIH 3D model repository (3DPX ID: 020598, Title: 3D Nasal Septum).

Human nasal cartilage: Functional properties and structure-function relationships for the development of tissue engineering design criteria.

Nose reconstruction often requires scarce cartilage grafts. Nasal cartilage properties must be determined to serve as design criteria for engineering grafts. Thus, mechanical and biochemical properties were obtained in multiple locations of human nasal septum, upper lateral cartilage (ULC), and lower lateral cartilage (LLC). Within each region, no statistical differences among locations were detected, but anisotropy at some septum locations was noted. In the LLC, the tensile modulus and ultimate tensile strength (UTS) in the inferior-superior direction were statistically greater than in the anterior-posterior direction. Cartilage from all regions exhibited hyperelasticity in tension, but regions varied in degree of hyalinicity (i.e., Col II:Col I ratio). The septum contained the most collagen II and least collagen I and III, making it more hyaline than the ULC and LLC. The septum had a greater aggregate modulus, UTS, and lower total collagen/wet weight (Col/WW) than the ULC and LLC. The ULC had greater tensile modulus, DNA/WW, and lower glycosaminoglycan/WW than the septum and LLC. The ULC had a greater pyridinoline/Col than the septum. Histological staining in all regions suggested the presence of chondrons in all regions. In the ULC and LLC, tensile modulus correlated with total collagen content, while aggregate modulus correlated with pyridinoline content and weakly with pentosidine content. However, future studies should be performed to validate these proposed structure-function relationships. This study of human nasal cartilage provides 1) crucial design criteria for nasal cartilage tissue engineering efforts, 2) quantification of major and minor collagen subtypes and crosslinks, and 3) structure-function relationships. Surprisingly, the large mechanical properties found, particularly in the septum, suggests that nasal cartilage may experience higher-than-expected mechanical loads. STATEMENT OF SIGNIFICANCE: While tissue engineering holds promise to generate much-needed cartilage grafts for nasal reconstruction, little is known about nasal cartilage from an engineering perspective. In this study, the mechanical and biochemical properties of the septum, upper lateral cartilage (ULC), and lower lateral cartilage (LLC) were evaluated using cartilage-specific methods. For the first time in this tissue, all major and minor collagens and collagen crosslinks were measured, demonstrating that the septum was more hyaline than the ULC and LLC. Additionally, new structure-function relationships in the ULC and LLC were identified. This study greatly expands upon the quantitative understanding of human nasal cartilage and provides crucial engineering design criteria for much-needed nasal cartilage tissue engineering efforts.

Nanoparticle based intranasal drug delivery system of some herbal medicinal plants for Alzheimer’s disease

AbstractBackgroundDiseases of the Central Nervous System (CNS) such as epilepsy, schizophrenia, meningitis, migraine, Parkinson’s disease and Alzheimer’s disease require delivery of the drug to the brain for effective treatment but it remains problematic area to deal with, as the central nervous system (CNS) is isolated from the whole body by the blood–brain barrier (BBB). This tight physiological barrier limits the drug diffusion towards the brain parenchyma and is considered as the bottleneck in brain drug development. Now this can be circumvented by intraventricular or intracerebral administration. Intra Nasal delivery thus attributes to non‐invasive, essentially painless, high vascularity and the permeability of the nasal mucosa, which aids the drug in bypassing the aforementioned processes of degradation. Now the increasing realization of the side effects of allopathic medicines, coupled with the growing awareness about the medicinal benefits as well as therapeutic effect of herbal products is pushing up the demand for herbal extracts and herbal‐based supplements worldwide.MethodIn this study we designed a natural compound based Nanoformulations for drug delivery via nasal route to treat Alzheimer’s conditionResultAfter various preliminary studies we prepared standard extract loaded Nanoformulations with their particle size between the range 80 – 290nm and sustained release kinetics profile. Further, the toxicity analysis (morphological, cell viability, cytotoxicity assays) of these nanoformulations was performed on RPMI2650 (Human nasal septum) and NB41A3 (Mouse hippocampus) cell lines based on the route and site of drug delivery. Lastly, in vivo experiments were performed with AD (cognitive impairment) induced mice model. There was seemingly, a significant decrease in anti ß amyloid antibody positive neurons in case of optimised nanoformulations in comparison to the galantamine. It was also found to have reduced lesions caused due to the amyloid aggregation reflecting a noted improvement in dispersing and reducing the lesions in the hippocampal tissues.ConclusionIn conclusion, the present study demonstrates that the developed nanoformulations have potential therapeutic effects on improving the pathological state of AD, and might be taken further as a promising candidate for clinical research to evaluate its efficacy in humans.

Septoplasty Training During the COVID-19 Era: Development and Validation of a Novel Low-Cost Simulation Model.

ObjectiveIn a context of increasingly limited surgical exposition, enhanced by the coronavirus disease 2019 (COVID-19) pandemic context, the objective of this article is to explain the development of a novel low-cost and simple replication animal-based septoplasty training model for otolaryngology residents, to assess its face and construct validity, and to validate a specific rating scale for each task.Study DesignExperimental study.SettingSurgical simulation laboratory.MethodsSeptoplasty experts divided the procedure into key tasks. A simulator model to perform tasks was developed using pig ears to imitate human nasal septum cartilage, and a Specific Rating Scale was constructed. Trainees and faculty performed all tasks in the model. The participants were videotaped, and operative time, hand movements, and path length were recorded using a motion sensor device. Two blinded experts evaluated the videos with Global and Specific Rating Scales. All participants answered a satisfaction survey.ResultsFifteen subjects were recruited (7 trainees and 8 faculty). Significantly higher Global Rating Scale score, shorter operative time and path length, and fewer hand movements were observed in the faculty group. The satisfaction survey showed high applicability to a real scenario (mean score of 4.6 out of 5). Specific Rating Scale showed construct and concurrent validity and high reliability.ConclusionThis simulation model and its specific rating scale can be accurately used as a validated surgical assessment tool for endonasal septoplasty skills. Its low cost and simple replicability make it a potentially useful tool in any otolaryngology surgical training program.

A compositional analysis of native and decellularized porcine nasal septum cartilage.

Decellularization of porcine septum cartilage is necessary for its application as xenogenic replacement material. The aim of this study was to investigate spatial differences of structure and composition in the whole native and decellularized porcine nasal septum. Subsequently, the results shall be compared with studies of human nasal septum. Ten porcine nasal septa were divided into six regions from caudal to cephalic and four regions from dorsal to ventral to create a grid of 24 approximately equal segments. All segments of five septal cartilages were decellularized separately by a wet chemical multistep procedure. The segments were analyzed to determine quantitative amounts of total collagen, chondrocytes, and sulfated glycosaminoglycans (sGAG). The distribution of cell number showed no significant differences between the individual regions. For the distribution of collagen and sGAG, no significant differences could be identified from caudal to cephalic, both in native and decellularized tissue. From dorsal to ventral, native and decellularized nasal septum showed significant differences between individual regions. In native septum, linear regression analysis indicated a decreasing collagen and an increasing sGAG content from dorsal to ventral. After decellularization, an increasing collagen and a decreasing sGAG content was detected. The results of this study showed slightly but significant differences in the distribution of collagen and sGAG from dorsal to ventral. From caudal to cephalic, no differences could be observed. Compared to human, nasal septum differences in cell, collagen, and sGAG content were detected. Despite this, human and porcine nasal septum showed similar distributions and a consistently inverse linearity of collagen and sGAG content. Nevertheless, the midcaudal and midcephalic regions showed the highest porosity and a high stability and thus offer the best conditions for the revitalization of porcine tissue by human cells.

The Releasate of Avascular Cartilage Demonstrates Inherent Pro-Angiogenic Properties In Vitro and In Vivo.

ObjectiveCartilage is avascular and numerous studies have identified the presence of single anti- and pro-angiogenic factors in cartilage. To better understand the maintenance hyaline cartilage, we assessed the angiogenic potential of complete cartilage releasate with functional assays in vitro and in vivo.DesignWe evaluated the gene expression profile of angiogenesis-related factors in healthy adult human articular cartilage with a transcriptome-wide analysis generated by next-generation RNAseq. The effect on angiogenesis of the releasate of cartilage tissue was assessed with a chick chorioallantoic membrane (CAM) assay as well as human umbilical vein endothelial cell (HUVEC) migration and proliferation assays using conditioned media generated from tissue-engineered cartilage derived from human articular and nasal septum chondrocytes as well as explants from bovine articular cartilage and human nasal septum. Experiments were done with triplicate samples of cartilage from 3 different donors.ResultsRNAseq data of 3 healthy human articular cartilage donors revealed that the majority of known angiogenesis-related factors expressed in healthy adult articular cartilage are pro-angiogenic. The releasate from generated cartilage as well as from tissue explants, demonstrated at least a 3.1-fold increase in HUVEC proliferation and migration indicating a pro-angiogenic effect of cartilage. Finally, the CAM assay demonstrated that cartilage explants can indeed attract vessels; however, their ingrowth was not observed.ConclusionUsing multiple approaches, we show that cartilage releasate has an inherent pro-angiogenic capacity. It remains vessel free due to anti-invasive properties associated with the tissue itself.

Is intranasal administration an opportunity for direct brain delivery of lacosamide?

Lacosamide is well-known as an effective and safe anticonvulsant drug. Nevertheless, there is also evidence of anti-epileptogenic, neuroprotective and antinociceptive properties of lacosamide. It is currently available as oral and intravenous (IV) formulations, and its brain concentrations and therapeutic effects depend on its passage across the blood-brain barrier (BBB). Therefore, to circumvent the restrictive BBB, we herein evaluated the intranasal (IN) administration of lacosamide.Nasal thermoreversible gels were screened in vitro for their influence on the viability of human nasal septum (RPMI 2650) and lung adenocarcinoma (Calu-3) cells. According to the Alamar Blue test, the in situ gel composed of Pluronic F-127 (22.5%, w/v) and Carbopol 974P (0.2%, w/v) did not affect cell viability, which remained higher than 85%, within the concentration range of lacosamide.The in situ gel was intranasally administered to healthy male CD-1 mice (8.33 mg/kg) to describe the pharmacokinetic profiles of lacosamide in plasma, brain, lung and kidney and compare them with those obtained after IV administration of the same dose.Accordingly, IN administration allowed a fast (tmax in plasma: 5 min) and complete systemic absorption of lacosamide (absolute bioavailability: 120.46%). Interestingly, IN lacosamide demonstrated higher exposure (given by the AUCt) in the brain (425.44 µg.min/mL versus 274.49 µg.min/mL), but lower exposure in kidneys (357.56 µg.min/mL versus 762.61 µg.min/mL), in comparison to IV administration. These findings, together with the tmax in brain of 15 min, a drug targeting efficiency (DTE) of 128.67% and a direct transport percentage of 22.28%, evidence that part of lacosamide reaches the brain directly after nasal administration, even though penetration into the brain from the systemic circulation seems to be the major determinant of brain exposure. Importantly, lacosamide concentrations found in lungs following IN administration were considerably higher than those observed after IV injection, until 30 min post-dosing (p < 0.05). Nevertheless, attained drug concentrations were lower than those tested in vitro in the Calu-3 cell line (1–100 µM), indicating that adverse effects are unlikely to occur in vivo.Hence, it seems that the proposed IN route has potential to be a suitable and valuable strategy for the brain delivery of lacosamide in emergency conditions and for the chronic treatment of epilepsy and other neurological diseases.

ANATOMICAL PECULIARITIES OF THE NASAL PASSAGES IN 7-8-WEEK PRE-FETUSES

In Ukraine due to an increasing harmful effect of environmental factors on the human organism, especially in the period of the intrauterine development, the problem has become an important issue. Investigation of the dynamics of changes in the topography of structures of organs and complexes of organs during the prenatal period of human ontogenesis with the aim to determine the interrelations and interaction of the shape-generating processes on the spatial-temporal orientation of the anatomical structures as well as finding the time and morphological preconditions of possible occurrence of variants in their structure and congenital defects is one of the important scientific directions in anatomical field. 10 specimens of the nasal area of 7-8week pre-fetuses, regularities of their development, formation and morphological transformations of the human nasal septum were examined by means of micro- and morphometry. During the pre-fetal period the rudiment of the nasal septum was found to be presented by the mesenchyme covered externally with the high columnar epithelium with the nuclei of a spherical or oval shape. The mesenchyme cells are located more densely in the central part of the nasal septum rudiment forming an aggregation. The anterior and median thirds of the nasal septum are merged with the primary palate, and its posterior part hangs down into the primary oral cavity. In pre-fetuses at the end of the 7th week of development (19,5-20,0 mm long) the subepithelial blood network is presented by the vascular columns of a capillary type 8,0±0,5 mcm in diameter. During the 8th week of the intrauterine life a layer of the subcartilaginous tissue appears in the central part of the nasal septum due to differentiation of the mesenchyme cells. The mesenchyme cells are concentrated directly near the lower part of the posterior third of the nasal septum looking like a pair formation in the form of laminae – vomer rudiment. At the end of the 8th week of the intrauterine development the subcartilaginous tissue of the nasal septum is transformed into the immature cartilaginous tissue. The rudiment of the cuneopalatine artery (24,0±0,5 mcm in diameter) is also determined in the posterior portion of the lateral wall of the primary nasal cavity.

In vitro characterization of physico-chemical properties, cytotoxicity, bioactivity of urea-crosslinked hyaluronic acid and sodium ascorbyl phosphate nasal powder formulation

An innovative lyophilized dry powder formulation consisting of urea-crosslinked hyaluronic acid (HA-CL) and sodium ascorbyl phosphate (SAP) – LYO HA-CL – SAP- was prepared and characterized in vitro for physico-chemical and biological properties. The aim was to understand if LYO HA-CL – SAP could be used as adjuvant treatment for nasal inflammatory diseases. LYO HA-CL – SAP was suitable for nasal delivery and showed to be not toxic on human nasal septum carcinoma-derived cells (RPMI 2650 cells) at the investigated concentrations. It displayed porous, polygonal particles with unimodal, narrow size distribution, mean geometric diameter of 328.3 ± 27.5 µm, that is appropriate for nasal deposition with no respirable fraction and 88.7% of particles with aerodynamic diameter >14.1 µm. Additionally, the formulation showed wound healing ability on RPMI 2650 cells, and reduced interleukin-8 (IL-8) level in primary nasal epithelial cells pre-induced with lipopolysaccharide (LPS). Transport study across RPMI 2650 cells showed that HA-CL could act not only as carrier for SAP and active ingredient itself, but potentially also as mucoadhesive agent. In conclusion, these results suggest that HA-CL and SAP had anti-inflammatory activity and acted in combination to accelerate wound healing. Therefore, LYO HA-CL – SAP could be a potential adjuvant in nasal anti-inflammatory formulations.

Histological Image Processing for the Assessment of Tissue Engineered Cartilage

Abstract In a recently developed perfusion bioreactor, human nasal septum chondrocytes were seeded on decellularized porcine collagen scaffolds and cultivated for 6 weeks. Afterwards, the samples were stained with alcian blue and multiple histological microscope images were taken to assess the migration of the human cells and their redifferentiation. In this paper, we propose an image processing algorithm to objectively quantify the cultivation results. This algorithm performs a white balance, detects cell nuclei and their migration depth, and detects lacunae and their orientation. To evaluate performance, sensitivity and precision are calculated using manually labeled data over 50 images. The detection of cell nuclei has a reasonable precision (73%), but the level of sensitivity (42%) should be further improved. The proposed method demonstrates acceptable level of precision (83%) and sensitivity (86%) for the detection of lacunae.

ANATOMICAL FEATURES OF THE HUMAN NASAL SEPTUM IN THE FIRST PERIOD OF MATURE AGE

With the purpose to examine age and vaiant anatomy of the nasal septum 10 macrospecimens of the human nasal septum at the first mature age were studied by means of morphological methods. The anterio-posterio size of the sptum in general was found to range between 64,0 to 78,0mm. Its largest vertical size does not exceed 48,0 mm. The mucous membrane is 0,8-1,0 mm thick. The epithelial layer is 36 and 54 mcm thick in the thickest and thinnest areas respectively. The mucous membrane is thick in the anterio-inferior part. Anterior-posterior size of the tetragonal lamina ranges from 24,0 to 38,0 mm. the vertical size close to the anterior end of the lamina is 21,0-30,0 mm, and closer to its posterios end – it is not larger than 16,0-20,0 mm. The osseous wall is 2,5-3,0 mm thick.

Successful Low-Cost Scaffold-Free Cartilage Tissue Engineering Using Human Cartilage Progenitor Cell Spheroids Formed by Micromolded Nonadhesive Hydrogel.

The scaffold-free tissue engineering using spheroids is pointed out as an approach for optimizing the delivery system of cartilage construct. In this study, we aimed to evaluate the micromolded nonadhesive hydrogel (MicroTissues®) for spheroid compaction (2-day culture) and spontaneous chondrogenesis (21-day culture) using cartilage progenitors cells (CPCs) from human nasal septum without chondrogenic stimulus. CPC spheroids showed diameter stability (486 μm ± 65), high percentage of viable cells (88.1 ± 2.1), and low percentage of apoptotic cells (2.3%). After spheroid compaction, the synthesis of TGF-β1, TGF-β2, and TGF-β3 was significantly higher compared to monolayer (p < 0.005). Biomechanical assay revealed that the maximum forces applied to spheroids after chondrogenesis were 2.6 times higher than for those cultured for 2 days. After spontaneous chondrogenesis, CPC spheroids were entirely positive for N-cadherin, collagen type II and type VI, and aggrecan and chondroitin sulfate. Comparing to monolayer, the expression of SOX5 and SOX6 genes analyzed by qPCR was significantly upregulated (p < 0.01). Finally, we observed the capacity of CPC spheroids starting to fuse. To the best of our knowledge, this is the first time in the scientific literature that human CPC spheroids were formed by micromolded nonadhesive hydrogel, achieving a successful scaffold-free cartilage engineering without chondrogenic stimulus (low cost).

Cytotoxicity of Different Excipients on RPMI 2650 Human Nasal Epithelial Cells.

The nasal route receives a great deal of attention as a non-invasive method for the systemic administration of drugs. For nasal delivery, specific formulations containing excipients are used. Because of the sensitive respiratory mucosa, not only the active ingredients, but also additives need to be tested in appropriate models for toxicity. The aim of the study was to measure the cytotoxicity of six pharmaceutical excipients, which could help to reach larger residence time, better permeability, and increased solubility dissolution rate. The following excipients were investigated on RPMI 2650 human nasal septum tumor epithelial cells: β-d-mannitol, sodium hyaluronate, α and β-cyclodextrin, polyvinyl alcohol and methylcellulose. 3-(4,5-dimethyltiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye conversion assay and real-time impedance analysis were used to investigate cytotoxicity. No excipient showed toxicity at 0.3% (w/v) concentration or below while 1% concentration a significantly reduced metabolic activity was measured by MTT assay for methylcellulose and cyclodextrins. Using impedance measurements, only β-cyclodextrin (1%) was toxic to cells. Mannitol at 1% concentration had a barrier opening effect on epithelial cells, but caused no cellular damage. Based on the results, all additives at 0.3%, sodium hyaluronate and polyvinyl alcohol at 1% concentrations can be safely used for nasal formulations.

Characterization of a migrative subpopulation of adult human nasoseptal chondrocytes with progenitor cell features and their potential for in vivo cartilage regeneration strategies.

BackgroundProgenitor cells display interesting features for tissue repair and reconstruction. In the last years, such cells have been identified in different cartilage types. In this study, we isolated a migrative subpopulation of adult human nasoseptal chondrocytes with progenitor cell features by outgrowth from human nasal septum cartilage. These putative progenitor cells were comparatively characterized with mesenchymal stem cells (MSC) and human nasal septum chondrocytes with respect to their cellular characteristics as well as surface marker profile using flow cytometric analyses. Differentiation capacity was evaluated on protein and gene expression levels.ResultsThe migrative subpopulation differentiated into osteogenic and chondrogenic lineages with distinct differences to chondrocytes and MSC. Cells of the migrative subpopulation showed an intermediate surface marker profile positioned between MSC and chondrocytes. Significant differences were found for CD9, CD29, CD44, CD90, CD105 and CD106. The cells possessed a high migratory ability in a Boyden chamber assay and responded to chemotactic stimulation. To evaluate their potential use in tissue engineering applications, a decellularized septal cartilage matrix was either seeded with cells from the migrative subpopulation or chondrocytes. Matrix production was demonstrated immunohistochemically and verified on gene expression level. Along with secretion of matrix metalloproteinases, cells of the migrative subpopulation migrated faster into the collagen matrix than chondrocytes, while synthesis of cartilage specific matrix was comparable.ConclusionsCells of the migrative subpopulation, due to their migratory characteristics, are a potential cell source for in vivo regeneration of nasal cartilage. The in vivo mobilization of nasal cartilage progenitor cells is envisioned to be the basis for in situ tissue engineering procedures, aiming at the use of unseeded biomaterials which are able to recruit local progenitor cells for cartilage regeneration.

Enhanced chondrogenesis of human nasal septum derived progenitors on nanofibrous scaffolds

Topographical cues can be exploited to regulate stem cell attachment, proliferation, differentiation and function in vitro and in vivo. In this study, we aimed to investigate the influence of different nanofibrous topographies on the chondrogenic differentiation potential of nasal septum derived progenitors (NSP) in vitro. Aligned and randomly oriented Ploy (l-lactide) (PLLA)/Polycaprolactone (PCL) hybrid scaffolds were fabricated via electrospinning. First, scaffolds were fully characterized, and then NSP were seeded on them to study their capacity to support stem cell attachment, proliferation and chondrogenic differentiation. Compared to randomly oriented nanofibers, aligned scaffolds showed a high degree of nanofiber alignment with much better tensile strength properties. Both scaffolds supported NSP adhesion, proliferation and chondrogenic differentiation. Despite the higher rate of cell proliferation on random scaffolds, a better chondrogenic differentiation was observed on aligned nanofibers as deduced from higher expression of chondrogenic markers such as collagen type II and aggrecan on aligned scaffolds. These findings demonstrate that electrospun constructs maintain NSP proliferation and differentiation, and that the aligned nanofibrous scaffolds can significantly enhance chondrogenic differentiation of nasal septum derived progenitors.

Improved Transnasal Transport and Brain Uptake of Tizanidine HCl-Loaded Thiolated Chitosan Nanoparticles for Alleviation of Pain

The aim of this study was to prepare and characterize thiolated chitosan (TC) nanoparticles (NPs) of tizanidine HCl (TZ) and to evaluate its transport across monolayer of RPMI 2650 cells (Human nasal septum carcinoma cell line) followed by assessment of their pharmacokinetic and pharmacodynamic attributes, after intranasal (i.n.) administration. Chitosan was thiolated by carbodiimide method and thiolation was confirmed qualitatively and quantitatively. NPs were prepared using ionotropic gelation and evaluated for mucoadhesion using sheep nasal mucosa for drug permeation and cytotoxicity using monolayer of RPMI 2650 cells. Drug biodistribution was evaluated after technetium-99m labeling, visualized using gamma camera, and evaluated pharmacodynamically by measuring antinociceptive activity in mice. High mucoadhesion and permeation of drug were observed for TC NPs with least toxicity to nasal epithelial cells. Brain uptake and antinociceptive effect of the drug were significantly enhanced after thiolation of chitosan. This concludes that TC NPs, after i.n. administration, show significant increase in the mucoadhesion, reduction in cytotoxicity, enhanced permeation across cells monolayer, higher TZ brain uptake, and considerable increase in antinociceptive activity of TZ in mice. These features make TC an interesting polymer for demonstrating appreciable improvement of transnasal permeation of hydrophilic drugs, such as TZ, known to have limited permeation across blood-brain barrier.

Cadmium-induced up-regulation of aldo–keto reductase 1C3 expression in human nasal septum carcinoma RPMI-2650 cells: Involvement of reactive oxygen species and phosphatidylinositol 3-kinase/Akt

Cadmium is a well-known toxic metal and occupational exposure to it is associated with lung cancer. In probing the possible non-genotoxic molecular targets of cadmium-induced nasal toxicity, we performed an mRNA differential display analysis for cadmium-treated human nasal septum carcinoma RPMI-2650 cells. Cadmium (≥0.5 μM) inhibited the cell proliferation. The intracellular ROS levels were induced by cadmium treatment. In addition, cadmium elicited the AKR1C3 expression. The cadmium-induced increase in AKR1C3 protein levels was suppressed by N-acetylcysteine (NAC) and, to a lesser extent, PI3K inhibitor (Ly294002). Cells pretreated with Ly294002 were more resistant to cadmium toxicity than control. The increase in AKR1C3 protein level was accompanied by an increase in the nuclear transcription factor Nrf2. Overall, our data suggest that cadmium-induced ROS cause up-regulation of AKR1C3 expression, at least partially via the activation of PI3K-related intracellular signaling pathways, and Nrf2 activation, thereby contributing to an adaptive intracellular response to cadmium toxicity.

Chondrocyte Viability in Human Nasal Septum After Morselization

Chondrocyte Viability in Human Nasal Septum After Morselization

Chondrocyte Viability in Human Nasal Septum After Morselization

Chondrocyte Viability in Human Nasal Septum After Morselization

Porous Poly(vinyl alcohol)-Alginate Gel Hybrid Construct for Neocartilage Formation Using Human Nasoseptal Cells

Limited options exist for the restoration of craniofacial cartilage. Autologous tissue or porous polyethylene is currently used for nasal and auricular reconstruction. Both options are associated with drawbacks, including donor site morbidity and implant extrusion. Poly(vinyl alcohol) (PVA) is a non-degradable flexible biocompatible polymer than can be engineered to mimic the properties of cartilage. The goal of this study was to engineer a biosynthetic hybrid construct using a combination of PVA-alginate hydrogels and human nasal septum chondrocytes. Chondrocytes isolated from human nasal septum cartilage were expanded and mixed with 2% sodium alginate hydrogel. The chondrocyte-alginate mix was injected into a non-degradable porous PVA hydrogel, creating biosynthetic constructs. A group of these constructs were implanted into the subcutaneous environment of nude mice, while the other group was cultured in a spinner flask bioreactor system for 10 d and then implanted. After 6 wk in vivo, the histologic, biochemical, and biomechanical properties were examined. Histological analysis demonstrated sulfated glycosaminoglycans and deposition of collagen type II in constructs from both groups. Constructs cultured in the bioreactor system prior in vivo implantation demonstrated higher levels of DNA, glycosaminoglycans, and hydroxyproline. An increase of 22% in the compressive strength of the engineered constructs exposed to the bioreactor was also observed. A novel porous PVA-alginate gel hybrid was used to successfully engineer human cartilage invivo. A 10-d period of bioreactor culturing increased levels of DNA, glycosaminoglycans, hydroxyproline, and the compressive modulus of the constructs.