Clinical features of chronic fungal rhinosinusitis in Korean geriatric and non-geriatric patients.

PURPOSE: Worldwide, the incidence of chronic fungal rhinosinusitis (CFRS) has increased. Although ageing leads to weakening of the immune system, which increases susceptibility to CFRS, the CFRS characteristics in geriatric patients are unclear. Therefore, we comparatively analysed the clinical characteristics of CFRS in geriatric and non-geriatric patients. METHODS: This retrospective analysis compared the demographics, rhinologic symptoms, multiple allergen simultaneous tests, olfactory function tests, paranasal sinus computed tomography findings, and outcomes of 131 patients with CFRS who underwent functional endoscopic sinus surgery and 131 enrolled patients were divided in geriatric (> 65 years) and non-geriatric (≤ 65 years) groups. RESULTS: Among the geriatric and non-geriatric participants (n = 65, 49.6% and n = 66, 50.4%, respectively), hypertension and diabetes mellitus were more common in the geriatric group. Demographics, including symptoms, showed no significant intergroup differences. Normosmia and hyposmia were significantly less prevalent, whereas phantosmia and parosmia were more prevalent in the geriatric group than in the non-geriatric group (p = 0.03 and p = 0.01, respectively). Sphenoidal sinus involvement was significantly higher in geriatric patients than in non-geriatric patients (p = 0.02). CONCLUSION: Based on greater sphenoidal sinus involvement, a deeper anatomical area is more vulnerable to fungal infection in the geriatric group than in the non-geriatric group. Increasing clinicians' awareness of CFRS in geriatric patients with olfactory dysfunction, including phantosmia and parosmia, is important for early intervention.

Pott Puffy Tumor Caused by Dental Infection: A Case Report and Literature Review.

ABSTRACT: Pott puffy tumor (PPT), first described by Sir Percivall Pott in 1760, is a rare clinical entity characterized by a subperiosteal abscess associated with osteomyelitis of the frontal bone caused by direct or hematogenous spread. Although rare in this modern age of antibiotics, this tumor usually occurs as a complication of sinusitis. Moreover, intracranial complications such as subdural abscess, meningitis, sinus thrombosis, or brain abscess can occur concomitantly with the underlying sinusitis, despite the administration of antibiotics. Herein, we present the case of a 48-year-old man who was diagnosed with PPT using computed tomography and treated medically and surgically. The infection remained uncontrollable after surgery and drain removal, owing to the persistence of the original dental focus of the infection. This case highlights the importance of treating the source of the infection in addition to the local area of inflammation, to facilitate complete infection control in PPT.

Can the sensitisation to staphylococcal enterotoxin predict the severity of chronic rhinosinusitis?

BACKGROUND: Evidence is accumulating that Staphylococcus aureus plays an important role as a disease modifier in upper and lower airway disease. We aimed to assess the association of staphylococcal enterotoxins (SEs) with allergic multimorbidity as well as the severity of chronic rhinosinusitis. METHODS: We retrospectively reviewed the medical records of 97 subjects aged 6 years or older between March 2018 and June 2019 and analysed symptom scores, computed tomography scores, serum IgE levels to SEs, serum total and specific IgE levels to inhalant allergens. To evaluate eosinophilic chronic rhinosinusitis (ECRS), we used refractory ECRS score from the Japanese epidemiological survey. RESULTS: Of the 97 patients enrolled, 29 (29.9%) were non-sensitised, 33 (34.0%) were mono-sensitised, and 35 (36.1%) were poly-sensitised. Sensitisation to SEs was closely associated with poly-sensitisation to inhalant allergens. SE-sensitised participants had higher median values for total and specific IgE levels to inhalant allergens than did non-SE-sensitised participants. SE sensitisation was associated with allergic multimorbidity and severe allergic diseases, such as ECRS. CONCLUSIONS: This preliminary study suggested that sensitisation to SEs may play a role in the initiation of type-2 inflammatory responses, such as allergic rhinitis, ECRS, and allergic multimorbidity. Furthermore, sensitisation to SEs correlated with the severity of ECRS.

Prospective assessment of gustatory function after radiotherapy for head and neck cancers.

BACKGROUND: Taste disorders are major causes of morbidity in patients undergoing head and neck irradiation. We quantitatively assessed the gustatory function of patients with head and neck cancers who underwent radiotherapy using recently developed standardised tools for measuring taste. METHODS: Twenty patients undergoing head and neck irradiation responded to a specific questionnaire and were assessed by olfactory and gustatory function tests. To assess changes over time, testing was performed before, immediately after, and at 2- and 4-week intervals following the start of radiotherapy. Concurrently, patients were evaluated for xerostomia from radiotherapy. RESULTS: A decrease in the taste recognition threshold was observed in the second week after the beginning of radiotherapy. The taste detection threshold improved within the 14th-18th week. Most affected patients demonstrated that their gustatory function primarily decreased independent of the olfactory function. Disturbances in taste were exponentially worsened beyond an accumulated dose of 30 Gy and involved all tastants. According to a multivariate analysis, radiation-induced taste impairment was not influenced by the degree of xerostomia. However, there was an association between the dose of irradiation and the severity of taste disturbance. CONCLUSIONS: In this preliminary study, we found that the taste function was worse 2 weeks after the start of radiotherapy and returned to pretreatment levels within 4.5 months. Taste disturbances were exponentially worse beyond an accumulated dose of 20 Gy. Taste dysfunction after radiotherapy was not influenced by the degree of xerostomia, whereas only the dose of irradiation was associated with the severity of taste dysfunction.

An absorbable thread suture technique to treat snoring.

We investigated a novel, minimally invasive surgery that uses an absorbable suture technique to treat snoring and mild obstructive sleep apnea. This simple procedure was developed to increase the stiffness of the soft palate and to promote uvula elevation with sutures. Thirty-five snorer and mild obstructive sleep apnea syndrome patients were included in this study. The palate was sutured with the newly developed technique. The results of our surgery were evaluated using polysomnography (PSG), the Epworth sleepiness scale (ESS), and a visual analogue scale (VAS) before surgery and 90 days after surgery. One year after surgery, telephone interviews were performed to assess patient satisfaction. Postoperative physical examinations of all patients showed increased stiffness of the soft palate and superiorly displaced uvula. These findings were consistent after the postoperative day 90. The patients' snoring symptoms and their bed partners' complaints, assessed by ESS and VAS, significantly improved compared to the pre-treatment value (p < 0.05). Additionally, the apnea-hypopnea index (AHI), assessed by PSG, was significantly improved compared to the pre-treatment value (p < 0.05). Based on the results from the telephone interviews analyzed 1 year after surgery, about 88 % of patients were satisfied with the outcome. This minimally invasive snoreplasty that uses absorbable suture material is an effective and simple procedure for treating snoring and mild obstructive sleep apnea.

Engraftment and regenerative effects of bone marrow stromal cell transplantation on damaged rat olfactory mucosa.

To develop a new therapeutic method to treat olfactory deficits, we investigated the engraftment and regenerative effects of transplanted bone marrow stromal cells (BMSCs) on damaged rat olfactory mucosa. To induce olfactory nerve degeneration, one side of the olfactory mucosa of Sprague-Dawley rats was damaged via Triton X-100 irrigation. Phosphate-buffered saline containing syngeneic BMSCs was injected into the olfactory mucosa for transplantation. PKH fluorescent cell dye labeling of BMSCs was used to monitor the transplanted cells. After transplantation of BMSCs, the thickness and regeneration of olfactory mucosa were analyzed using hematoxylin-eosin (H&E) staining. S100 immunohistochemical staining was used to measure nerve sheath regeneration. The increase in NGF (nerve growth factor) level in the olfactory mucosa was measured by Western blot analysis. Transplanted bone marrow stromal cells were engrafted to the lamia propria of damaged mucosa. The mean time for normalization of thickness and morphological recovery of the olfactory mucosa was 4 weeks in the therapeutic group and 9 weeks in the control group. S100 immunoreactivity was higher on the BMSC-treated side than on the control side. During regeneration, the expression of NGF increased in the olfactory mucosa of the experimental group. Based on these results, BMSC transplantation accelerated regeneration of olfactory mucosa damaged by Triton X-100, and NGF may be essential to this regenerative process.

The effect of rat bone marrow derived mesenchymal stem cells transplantation for restoration of olfactory disorder.

The purpose of the study was to investigate the effect of bone marrow-derived mesenchymal stem cells (BMSCs) transplantation on olfactory epithelium (OE) of morphologic and functional restoration following neural Sensorineural Disorder in rats. Except the Normal group, twenty-one rats underwent Triton X-100 (TX-100) irrigation to induce degeneration of OE, and then BMSCs and PBS were treated from the both medial canthus to the rear part of the both nasal cavity into the experimental group and then were observed for restoration according to time point. At two and four weeks after transplantation with BMSCs, restoration of OE was observed with olfactory marker protein (OMP) and behavioral test. And we observed the expression of OMP, nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF). After TX-100 irrigation, the OE almost disappeared in 3 days. At four weeks after transplantation with BMSCs, the thickness and cellular composition of OE was considerably restored to normal group and expression of OMP was markedly increased when compared with PBS group and reduced the searching time in the behavioral test. Furthermore at two weeks after treatment with BMSCs, expression of NGF and BDNF was greatly increased when compared with PBS group. However at four weeks after treatment with BMSCs, expression of NGF and BDNF was slightly decreased. Our results suggest the BMSCs transplantation affect restoration of OE and olfaction, most likely via regulation of the neurotrophic factor expression, especially the expression of NGF and BDNF and has a possibility of a new therapeutic strategy for the treatment of olfactory disorder caused by the degeneration of OE.

Association of hearing impairment with chronic kidney disease: a cross-sectional study of the Korean general population.

BACKGROUND: We aimed to evaluate the association between hearing impairment and the prevalence of chronic kidney disease (CKD) in the largest population-based cross-sectional study to date. METHODS: This cross-sectional study was based on the Korean National Health and Nutritional Examination Survey (KNHANES). It included 5226 participants ≥19 years of age whose estimated glomerular filtration rate (eGFR) and hearing threshold had been measured. We diagnosed CKD as an eGFR <60 mL/min/1.73 m(2). The participants were also evaluated for the presence of other contributing factors related to kidney dysfunction. We divided the participants at the 40-dB threshold into hearing-impairment and no-hearing-impairment groups, using the average threshold of all six frequencies (500, 1000, 2000, 3000, 4000, and 6000 Hz) for both ears. RESULTS: The odds of hearing impairment was 1.25 times higher (95 % confidence interval: 1.12-1.64, p-value < 0.001) in participants with an eGFR <60 mL/min/1.73 m(2) than in those with an eGFR ≥60 mL/min/1.73 m(2) after adjustments for age, sex, smoking, alcohol, body mass index, diabetes mellitus, hypertension, dyslipidemia, and microalbuminuria. Among the risk parameters of CKD associated with hearing impairment, linear regression analysis adjusted for age and sex determined that each increase of serum creatinine or blood pressure was positively associated with an increase in hearing threshold (p-value < 0.01). CONCLUSION: The odds of hearing impairment were greater with lower eGFR than with normal eGFR. Individuals with CKD were more likely to also have hearing impairment. We recommend screening the hearing of patients with CKD to provide earlier identification of hearing impairment and earlier intervention, thereby preventing progression of hearing impairment and providing appropriate treatment strategies.

Carbon monoxide poisoning-induced encephalopathy in a carbon dioxide arc welder: a case report.

Background: It is widely known that carbon dioxide (CO2) arc welding generates carbon monoxide (CO). However, to the best of our knowledge, no case reports have been published regarding CO poisoning in CO2 arc welders. Therefore, we aimed to report a case of CO poisoning-induced encephalopathy in a CO2 arc welder in the Republic of Korea to inform about the dangers of CO exposure among CO2arc welders. Case presentation: A 40-year-old man working as a CO2 arc welder for 15 years visited a local hospital with a tremor, involuntary urination, and speaking gibberish, on April 9, 2019. He stated that he had intermittent headache and forgetting symptoms for the last 5 years, and had been lost on the way to work several times. On April 9, 2019, he was diagnosed with CO poisoning-induced encephalopathy through brain magnetic resonance imaging. He received hyperbaric oxygen therapy, and some of his symptoms improved. According to the exposure assessment of his work environment, he was continuously exposed to high concentrations of CO for 15 years while operating CO2 arc welding machines. Conclusions: After evaluating the patient's work environment and evaluating his medical history, we concluded that his encephalopathy was caused by CO exposure during CO2 arc welding. Thus CO2 arc welders must be aware of the risk of CO poisoning and strive to avoid CO exposure.

Vulnerable Factors Affecting Urinary N-Methylformamide Concentration among Migrant Workers in Manufacturing Industries in Comparison with Native Workers in the Republic of Korea (2012-2019).

BACKGROUND: Occupational studies on N-N-dimethylformamide (DMF) exposure among migrant workers in Korea are scarce. We determined the urine concentration of N-methylformamide (NMF) among migrant workers with DMF exposure and compared the data with those of native workers. METHODS: Data were collected from Workers' Special Health Examination and Work Environment Monitoring databases during 2014-2019. Workers aged ≥20 years were eligible to participate in the special health examination for DMF exposure. Urine concentrations of NMF were determined and compared between migrant and native workers. We also evaluated the factors affecting the difference in the urine concentration of NMF between the migrant and native workers. Multiple logistic regression was performed by adding confounders step by step. RESULTS: Among 9259 subjects, 504 (5.2%) were migrant workers. The mean urinary concentration of NMF was 6.73 mg/L in migrant workers, which was significantly higher than that in native workers (2.06 mg/L, p < 0.001). The odds of a urine concentration of NMF > 30 mg/L were significantly higher in migrant workers than in native workers after adjusting for sex and age (odds ratio [OR] = 7.31, 95% confidence interval [CI] = 4.66-11.45). However, the odds between the native and migrant workers were not significantly different when fully adjusted for confounders (OR = 1.12, 95% CI = 0.65-1.94). CONCLUSIONS: The excessive exposure to DMF among migrant workers was attributed not to differences in biological characteristics but to their work environment. Workers must have awareness of the use of protective equipment and knowledge of hazardous chemicals that they may be exposed to, especially at the workplace.

Nasopharyngeal Tuberculosis with Concomitant Middle Ear Tuberculosis: A Case Report and Literature Review.

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (MTB), can affect the lungs (pulmonary TB) as well as other sites (extrapulmonary TB). Nasopharyngeal tuberculosis (NPTB) is a rare type of extrapulmonary TB. Since NPTB has nonspecific clinical presentation with low index of suspicion, it is difficult for clinicians to make an early diagnosis and proper treatment. We recently encountered a 42-year-old woman with NPTB concomitant with middle ear TB, which strongly mimicked nasopharyngeal carcinoma. Since the diagnosis of NPTB was difficult to confirm based on endoscopic findings and imaging studies, this patient underwent nasopharyngeal biopsy, and finally, polymerase chain reaction (PCR) confirmed NPTB. This report describes our NPTB case as well as summarizes all cases of NPTB reported in South Korea. We highlight that active tissue biopsy with antibacterial smear and additional PCR or specific TB blood test should be considered for cases with high suspicion of NPTB.

Assessment of risks for breast cancer in a flight attendant exposed to night shift work and cosmic ionizing radiation: a case report.

Background: Some epidemiological studies have estimated exposure among flight attendants with and without breast cancer. However, it is difficult to find a quantitative evaluation of occupational exposure factors related to cancer development individually in the case of breast cancer in flight attendants. That is, most, if not all, epidemiological studies of breast cancer in flight attendants with quantitative exposure estimates have estimated exposure in the absence of individual flight history data. Case presentation: A 41-year-old woman visited the hospital due to a left breast mass after a regular check-up. Breast cancer was suspected on ultrasonography. Following core biopsy, she underwent various imaging modalities. She was diagnosed invasive ductal carcinoma of no special type (estrogen receptor positive in 90%, progesterone receptor positive in 3%, human epidermal growth factor receptor 2/neu equivocal) with histologic grade 3 and nuclear grade 3 in the left breast. Neoadjuvant chemotherapy was administered to reduce the tumor size before surgery. However, due to serious chemotherapy side effects, the patient opted for alternative and integrative therapies. She joined the airline in January, 1996. Out of all flights, international flights and night flights accounted for 94.9% and 26.2, respectively. Night flights were conducted at least four times per month. Moreover, based on the virtual computer program CARI-6M, the estimated dose of cosmic radiation exposure was 78.81 mSv. There were no other personal triggers or family history of breast cancer. Conclusions: This case report shows that the potentially causal relationship between occupational harmful factors and the incidence of breast cancer may become more pronounced when night shift workers who work continuously are exposed to cosmic ionizing radiation. Therefore, close attention and efforts are needed to adjust night shift work schedules and regulate cosmic ionizing radiation exposure.

Integrated bioinformatic analysis of gene expression profiling data to identify combinatorial biomarkers in inflammatory skin disease.

Selection of appropriate biomarker to identify inflammatory skin diseases is complicated by the involvement of thousands of differentially expressed genes (DEGs) across multiple cell types and organs. This study aimed to identify combinatorial biomarkers in inflammatory skin diseases. From one gene expression microarray profiling dataset, we performed bioinformatic analyses on dataset from lesional skin biopsies of patients with inflammatory skin diseases (atopic dermatitis [AD], contact eczema [KE], lichen planus [Li], psoriasis vulgaris [Pso]) and healthy controls to identify the involved pathways, predict upstream regulators, and potential measurable extracellular biomarkers. Overall, 434, 629, 581, and 738 DEGs were mapped in AD, KE, Li, and Pso, respectively; 238 identified DEGs were shared among four different inflammatory skin diseases. Bioinformatic analysis on four inflammatory skin diseases showed significant activation of pathways with known pathogenic relevance. Common upstream regulators, with upregulated predicted activity, identified were CNR1 and BMP4. We found the following common serum biomarkers: ACR, APOE, ASIP, CRISP1, DKK1, IL12B, IL9, MANF, MDK, NRTN, PCSK5, and VEGFC. Considerable differences of gene expression changes, involved pathways, upstream regulators, and biomarkers were found in different inflammatory skin diseases. Integrated bioinformatic analysis identified 12 potential common biomarkers of inflammatory skin diseases requiring further evaluation.

Occurrence of a postoperative maxillary mucocele 20 years after orbital wall reconstruction.

Mucoceles of the paranasal sinus are epithelial-lined cystic structures filled with mucus and have multiple etiologies, including recurrent inflammation, trauma, or intrinsic disease. Particularly, a postoperative maxillary mucocele (POMM) is a delayed complication of radical surgery of the maxillary sinus, and most cases occur after Caldwell-Luc operations. Patients mainly complain of facial swelling, toothache, and tenderness. POMM has rarely been reported from other causes; however, there have been no reports on the occurrence of POMM following orbital wall reconstruction. Herein, we report a case of a patient with a POMM that developed 20 years after the aforementioned surgery. The patient complained of facial pain with visual disturbance, and underwent marsupialization using a combination of sublabial and endoscopic approaches, and the symptoms improved without recurrence.

Epithelial-myoepithelial carcinoma originating from a minor salivary gland in the nasal septum: A case report and literature review.

RATIONALE: Epithelial-myoepithelial carcinoma is an extremely rare, malignant neoplasm that occurs most frequently in the major salivary glands and accounts for approximately 1% of all salivary gland neoplasms. Few reports have described the presence of epithelial-myoepithelial carcinoma in the sinonasal region; hence, the treatment guideline and prognosis remain unclear. PATIENT CONCERNS: We reported a case of a 75-year-old woman with complaint of nasal obstruction and frequent epistaxis for 3 years. During the nasal endoscopic examination, a mass in the left nasal cavity originating from the left nasal septum that caused bleeding on touch was observed. DIAGNOSES: A diagnosis of epithelial-myoepithelial carcinoma was made based on the features of histopathology and immunohistochemistry of the surgical specimens. The patient was treated by surgical removal of the septal mass using the endonasal endoscopic approach. OUTCOMES: In the serial follow-up paranasal sinus imaging and endoscopic inspection, evidence of recurrence was absent for 18 months after surgery. LESSONS: This report highlights a case of epithelial-myoepithelial carcinoma originating from a minor salivary gland in the nasal septum, one of the most unusual locations. Diagnosis of epithelial-myoepithelial carcinoma should be made based on the findings of immunohistochemistry of the operative specimen. Clinicians should consider complete surgical resection as the effective treatment of choice.

Prevalence and Risk Factors of Chronic Rhinosinusitis in the Elderly Population of Korea.

BACKGROUND: Although a significant number of the clinical features and pathophysiologic mechanisms of chronic rhinosinusitis (CRS) have been described, only a few studies have been published on characterization of CRS in the field of aging. OBJECTIVE: We investigated the prevalence and risk factors of CRS in elderly (≥65 years old) Koreans using large-scale nationwide epidemiological data and compared the risk factors of elderly with those of younger adult participants (19-64 years old). METHODS: Data from 25 529 participants who completed the 2008-2012 Korean National Health and Nutrition Examination Survey were analyzed. Diagnosis of CRS was done according to the EP3OS 2012 guideline for epidemiologic study. Risk factors of CRS were compared in the aspects of sociodemographics, general health behaviors, clinical characteristics, and comorbidities of participants. RESULTS: The prevalence of CRS was significantly higher in 5590 elderly than in 19 939 younger adults (6.55% vs 5.69%; P = .016. Some variables of socioeconomic status and mental health in the adult group were associated with increased risk of CRS but did not show association in the elderly group. We observed a significant association between CRS prevalence and comorbid allergic rhinitis, asthma, and atopic dermatitis in both groups ( P < .05). However, in the elderly group, the associations were significantly weaker with regard to allergic rhinitis ( P-interaction = .03) and asthma ( P-interaction = .002). CONCLUSION: These results suggest that elderly populations have distinct pathophysiology and clinical presentations from adult CRS, and management for elderly patients with CRS may require different or additional therapeutic approaches.

Three Cases of Primary Ciliary Dyskinesia Combined With Reduced Exhaled Nitric Oxide.

OBJECTIVES: The diagnosis of primary ciliary dyskinesia (PCD) is often delayed in part related to the limitations of the available diagnostic tests. We present 3 cases of PCD diagnosed using an exhaled nitric oxide (eNO) measurement. METHODS: Three cases with a clinical phenotype consistent with PCD were evaluated using an eNO assay with additional transmission electron microscopy (TEM) and/or genetic panel testing. RESULTS: One male and 2 female patients presented with common symptoms included recurrent respiratory infection from early childhood and a history of neonatal respiratory distress as term newborn. Two of them had situs inversus totalis. Fractional eNO measurement revealed extremely low NO levels, and subsequently, TEM analysis confirmed ciliary ultrastructural defects in all patients. One patient had compound heterozygous mutation of the PCD-causative gene (DNAH5) identified using next generation sequencing. CONCLUSION: Our report stresses the reliability of eNO measurement in the diagnosis of PCD, accompanied by clinical phenotypes and additional diagnostic tools, such as TEM analysis and genetic testing.

Eosinophil extracellular trap formation is closely associated with disease severity in chronic rhinosinusitis regardless of nasal polyp status.

Chronic rhinosinusitis (CRS) is a heterogeneous inflammatory airway disease involving non-eosinophilic and eosinophilic phenotypes, which translate to various endotypes. Activated eosinophils and neutrophils are known to generate extracellular traps consisting of DNA and cytotoxic granule proteins. We sought to investigate the presence of eosinophil and neutrophil extracellular traps (EETs and NETs, respectively) in human CRS tissues and to clarify the associations with their clinical features. Nasal polyp (NP) or ethmoid tissue slides of 43 subjects from endoscopic sinus surgery for CRS were analysed. Quantitative analysis of EETs and NETs was performed by confocal microscopy using immunofluorescent staining. For correlation study, the presence of NPs, number of infiltrating tissue eosinophils, preoperative Lund-Mackay scores, and other comorbidities were analysed. EET formation was observed to varying degrees in all CRS groups and was correlated with the number of tissue eosinophils (r = 0.83, p < 0.001) regardless of the presence of NPs. Patients with more EETs demonstrated higher Lund-Mackay scores (r  =  0.51, p  = 0.009), blood eosinophilia (r  =  0.80, p  < 0.001), and decreased olfactory function (r  = -0.65, p  < 0.001). No correlation between the extent of EET formation and the presence of atopy or asthma was apparent. However, none of the CRS groups containing neutrophils formed NETs in this study. Eosinophilic CRS indicates the presence of EETs. Formation of EETs could have a role in clinical decision-making and prediction of treatment outcome of CRS, regardless of NP status.

Tissue-engineered bone formation with gene transfer and mesenchymal stem cells in a minimally invasive technique.

BACKGROUND: The objective of this study was to use a chitosan-alginate gel to implant bone marrow-derived mesenchymal stem cells subcutaneously in a minimally invasive manner and promote bone formation by the simultaneously transferred osteogenic protein (OP)-1 (bone morphogenic protein-7) gene. METHOD AND RESULTS: The complex of polyethylenimine/luciferase plasmid DNA embedded in the gel was able to transfect HEK 293 cells on a culture dish or co-encapsulated in the gel. When injected into the subcutaneous space of mice, luciferase expression was two to three orders of magnitude increased above the background. To examine the efficacy of gene-, cell-, and combined gene- and cell-encapsulated gels in tissue generation, samples were injected into the subcutaneous space of 6-week-old athymic nude mice, and the OP-1 plasmid was studied. At 8 weeks after the injection, the gels only maintained their volumetric shape when human mesenchymal stem cells (hMSCs) were encapsulated, but otherwise the gels were partially dissolved. Transgene expression of OP-1 was clearly detected in the samples after 4 weeks but not after 8 weeks. Type II collagen was detected in all the gels containing the OP-1 plasmid, with or without hMSCs. The samples with the combination of OP-1 DNA and hMSCs revealed strong type II collagen expression as well as osteoid foci. CONCLUSION: These results suggest that combined gene and hMSC delivery within a chitosan-alginate gel could be an interesting approach for tissue engineering.