1.Efficient Treatment of Psoriasis Using Conditioned Media from Mesenchymal Stem Cell Spheroids Cultured to Produce Transforming Growth Factor-β1-Enriched Small-Sized Extracellular Vesicles
Myeongjin SONG ; Kyung Min LIM ; Kwonwoo SONG ; Geun-Ho KANG ; Se Jong KIM ; Youngseo LEE ; Sujin YU ; Ki-Heon JEONG ; Ssang-Goo CHO
International Journal of Stem Cells 2024;17(4):407-417
Psoriasis is a common chronic inflammatory disease in which keratinocytes proliferate abnormally due to excessive immune action. Psoriasis can be associated with various comorbidities and has a significant impact on health-related quality of life. Although many systemic treatments, including biologic agents, have been developed, topical treatment remains the main option for psoriasis management. Consequently, there is an urgent need to develop topical treatments with minimal side effects and high efficacy. Mesenchymal stem cells (MSCs) exhibit excellent immune regulation, anti-inflammatory activities, and therapeutic effects, and MSC-derived extracellular vesicles (EVs) can serve as crucial mediators of functional transfer from MSCs. Therefore, this study aimed to develop a safe and easy-to-use emulsion cream for treating psoriasis using MSC conditioned media (CM) containing EVs. We developed an enhanced Wharton’s jelly MSC (WJ-MSC) culture method through a three-dimensional (3D) culture containing exogenous transforming growth factor-β3. Using the 3D culture system, we obtained CM from WJ-MSCs, which yielded a higher EV production compared to that of conventional WJ-MSC culture methods, and investigated the effect of EV-enriched 3D-WJMSC-CM cream on psoriasis-related inflammation. Administration of the EV-enriched 3D-WJ-MSC-CM cream significantly reduced erythema, thickness, and scaling of skin lesions, alleviated imiquimod-induced psoriasiform lesions in mice, and ameliorated histopathological changes in mouse skin. The upregulated mRNA expression of inflammatory cytokines, including IL-17a, IL-22, IL-23, and IL-36, decreased in the lesions. In conclusion, we present here a new topical treatment for psoriasis using an MSC EV-enriched cream.
2.Efficient Treatment of Psoriasis Using Conditioned Media from Mesenchymal Stem Cell Spheroids Cultured to Produce Transforming Growth Factor-β1-Enriched Small-Sized Extracellular Vesicles
Myeongjin SONG ; Kyung Min LIM ; Kwonwoo SONG ; Geun-Ho KANG ; Se Jong KIM ; Youngseo LEE ; Sujin YU ; Ki-Heon JEONG ; Ssang-Goo CHO
International Journal of Stem Cells 2024;17(4):407-417
Psoriasis is a common chronic inflammatory disease in which keratinocytes proliferate abnormally due to excessive immune action. Psoriasis can be associated with various comorbidities and has a significant impact on health-related quality of life. Although many systemic treatments, including biologic agents, have been developed, topical treatment remains the main option for psoriasis management. Consequently, there is an urgent need to develop topical treatments with minimal side effects and high efficacy. Mesenchymal stem cells (MSCs) exhibit excellent immune regulation, anti-inflammatory activities, and therapeutic effects, and MSC-derived extracellular vesicles (EVs) can serve as crucial mediators of functional transfer from MSCs. Therefore, this study aimed to develop a safe and easy-to-use emulsion cream for treating psoriasis using MSC conditioned media (CM) containing EVs. We developed an enhanced Wharton’s jelly MSC (WJ-MSC) culture method through a three-dimensional (3D) culture containing exogenous transforming growth factor-β3. Using the 3D culture system, we obtained CM from WJ-MSCs, which yielded a higher EV production compared to that of conventional WJ-MSC culture methods, and investigated the effect of EV-enriched 3D-WJMSC-CM cream on psoriasis-related inflammation. Administration of the EV-enriched 3D-WJ-MSC-CM cream significantly reduced erythema, thickness, and scaling of skin lesions, alleviated imiquimod-induced psoriasiform lesions in mice, and ameliorated histopathological changes in mouse skin. The upregulated mRNA expression of inflammatory cytokines, including IL-17a, IL-22, IL-23, and IL-36, decreased in the lesions. In conclusion, we present here a new topical treatment for psoriasis using an MSC EV-enriched cream.
3.Efficient Treatment of Psoriasis Using Conditioned Media from Mesenchymal Stem Cell Spheroids Cultured to Produce Transforming Growth Factor-β1-Enriched Small-Sized Extracellular Vesicles
Myeongjin SONG ; Kyung Min LIM ; Kwonwoo SONG ; Geun-Ho KANG ; Se Jong KIM ; Youngseo LEE ; Sujin YU ; Ki-Heon JEONG ; Ssang-Goo CHO
International Journal of Stem Cells 2024;17(4):407-417
Psoriasis is a common chronic inflammatory disease in which keratinocytes proliferate abnormally due to excessive immune action. Psoriasis can be associated with various comorbidities and has a significant impact on health-related quality of life. Although many systemic treatments, including biologic agents, have been developed, topical treatment remains the main option for psoriasis management. Consequently, there is an urgent need to develop topical treatments with minimal side effects and high efficacy. Mesenchymal stem cells (MSCs) exhibit excellent immune regulation, anti-inflammatory activities, and therapeutic effects, and MSC-derived extracellular vesicles (EVs) can serve as crucial mediators of functional transfer from MSCs. Therefore, this study aimed to develop a safe and easy-to-use emulsion cream for treating psoriasis using MSC conditioned media (CM) containing EVs. We developed an enhanced Wharton’s jelly MSC (WJ-MSC) culture method through a three-dimensional (3D) culture containing exogenous transforming growth factor-β3. Using the 3D culture system, we obtained CM from WJ-MSCs, which yielded a higher EV production compared to that of conventional WJ-MSC culture methods, and investigated the effect of EV-enriched 3D-WJMSC-CM cream on psoriasis-related inflammation. Administration of the EV-enriched 3D-WJ-MSC-CM cream significantly reduced erythema, thickness, and scaling of skin lesions, alleviated imiquimod-induced psoriasiform lesions in mice, and ameliorated histopathological changes in mouse skin. The upregulated mRNA expression of inflammatory cytokines, including IL-17a, IL-22, IL-23, and IL-36, decreased in the lesions. In conclusion, we present here a new topical treatment for psoriasis using an MSC EV-enriched cream.
4.Immune Cells Are DifferentiallyAffected by SARS-CoV-2 Viral Loads in K18-hACE2 Mice
Jung Ah KIM ; Sung-Hee KIM ; Jeong Jin KIM ; Hyuna NOH ; Su-bin LEE ; Haengdueng JEONG ; Jiseon KIM ; Donghun JEON ; Jung Seon SEO ; Dain ON ; Suhyeon YOON ; Sang Gyu LEE ; Youn Woo LEE ; Hui Jeong JANG ; In Ho PARK ; Jooyeon OH ; Sang-Hyuk SEOK ; Yu Jin LEE ; Seung-Min HONG ; Se-Hee AN ; Joon-Yong BAE ; Jung-ah CHOI ; Seo Yeon KIM ; Young Been KIM ; Ji-Yeon HWANG ; Hyo-Jung LEE ; Hong Bin KIM ; Dae Gwin JEONG ; Daesub SONG ; Manki SONG ; Man-Seong PARK ; Kang-Seuk CHOI ; Jun Won PARK ; Jun-Won YUN ; Jeon-Soo SHIN ; Ho-Young LEE ; Ho-Keun KWON ; Jun-Young SEO ; Ki Taek NAM ; Heon Yung GEE ; Je Kyung SEONG
Immune Network 2024;24(2):e7-
Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019.In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virusinfected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.
6.Efficacy and Safety of Guselkumab for Moderate to Severe Psoriasis in Korea:A Retrospective Study
Seung-Min OH ; Kyong-Won KANG ; Ki-Heon JEONG
Korean Journal of Dermatology 2023;61(4):217-225
Background:
Guselkumab is a monoclonal antibody that selectively targets interleukin-23 in the treatment of moderate to severe psoriasis. Several multinational clinical studies have reported on its efficacy. However, data on its efficacy and safety in Korean patients are currently very limited.
Objective:
This study evaluated the real-world efficacy and safety of guselkumab for treating patients with moderate to severe psoriasis in Korea.
Methods:
This single-center retrospective study included 40 patients treated with guselkumab for at least 12 weeks.Electronic medical records were reviewed for demographics, clinical characteristics, psoriasis area and severity index (PASI) score, body surface area, and adverse events.
Results:
The average PASI score at baseline (12.0±8.3) was significantly reduced to 3.3±3.8 at week 12, 2.2±2.2 at week 36, and 1.6±1.5 at week 52. At week 60, 93%, 60%, and 33% of patients achieved a PASI of 75, 90, and 100, respectively. Obesity, psoriatic arthritis, and previous biologics treatment experience were not significant indicators of guselkumab treatment efficacy. Seven patients reported adverse events; however, none discontinued guselkumab treatment.
Conclusion
Guselkumab is an effective and safe treatment option for moderate to severe psoriasis in Korea.
7.A Survey on the Perception and Behavior Regarding Tinea Pedis among Korean Adults
Minkyung CHO ; Yang Won LEE ; Dong Hun LEE ; Ki-Heon JEONG ; Soon Hyo KWON ; Jung Eun KIM ; Hyojin KIM ; Chan Ho NA ; Hyun-Min SEO ; Min Kyung SHIN ; Jiyoung AHN ; Yu Ri WOO ; Ga-Young LEE ; Yong Hyun JANG ; Hye Jung JUNG ; Yu Sung CHOI ; Tae Young HAN ; Ha-Eun LEE ; Chan Yl BANG ; Mi Woo LEE ; Dong Hyun KIM
Korean Journal of Dermatology 2023;61(7):420-428
Background:
Dermatophyte infection is one of the most common skin diseases affecting the skin, hair, and nails. Despite widespread recognition of the disease, missing details and misperceptions are commonplace in the general population.
Objective:
This study aimed to investigate the public perception and behavior regarding dermatophytosis of the hands and feet.
Methods:
This results from an online survey conducted between July 2022 and August 2022. The survey included 1,000 Korean participants aged 20 to 69 years, of whom 60% experienced symptoms of tinea pedis or onychomycosis. The questionnaire focused on the awareness and personal experience of tinea pedis and perception of the treatment of dermatophytosis.
Results:
Of the 1,000 participants, nearly 80% regarded tinea pedis as a common skin condition by which anyone can be affected. Furthermore, 88.4% had heard that the treatment of tinea pedis could be harmful, causing skin rash (60.4%) and worsening liver function (48.5%). Among 896 participants who noticed suspicious symptoms, 81.2% did not visit the clinic because it was not severe (50.1%) and seemed easily manageable (25.7%). Of the respondents, 84.4% preferred to meet dermatologists rather than non-dermatologist doctors regarding skin diseases, mainly because of trust in experts and belief in a faster cure.
Conclusion
Providing accurate and detailed information via online media, educational campaigns, and medical papers can rectify misconceptions and improve patient appliance, contributing to public skin health.
8.Risk of cancer, cardiovascular disease, thromboembolism, and mortality in patients with rheumatoid arthritis receiving Janus kinase inhibitors: a real-world retrospective observational study using Korean health insurance data
Hong Ki MIN ; Hyeongsu KIM ; Ho Jin JEONG ; Se Hee KIM ; Hae-Rim KIM ; Sang-Heon LEE ; KunSei LEE ; Soon-Ae SHIN ; Jong Heon PARK
Epidemiology and Health 2023;45(1):e2023045-
OBJECTIVES:
This study investigated whether Janus kinase inhibitors (JAKis) raise the risk of cardiovascular disease (CVD), venous thromboembolism (VTE), and cancer in patients with rheumatoid arthritis (RA).
METHODS:
We conducted a real-world retrospective observational study using data obtained from the Korean National Health Insurance Service database. Two data sets were analyzed: tumor necrosis factor inhibitor (TNFi)/JAKi-naive RA patients (set 1) and all RA patients who used TNFis or JAKis (set 2). The incidence rate ratios (IRRs) and hazard ratios (HRs) for acute myocardial infarction (AMI), stroke, cardiovascular (CV)-related mortality, major adverse cardiovascular events (MACE), VTE, arterial thromboembolism (ATE), cancer, and all-cause mortality were compared between the JAKi and TNFi groups.
RESULTS:
Set 1 included 1,596 RA patients (JAKi group: 645; TNFi group: 951), and set 2 included 11,765 RA patients (JAKi group: 2,498; TNFi group: 9,267). No adverse events (AEs) showed significantly higher IRRs in the JAKi groups than in the TNFi groups of sets 1 and 2. The HRs for MACE in the JAKi groups of sets 1 and 2 were 0.59 (95% confidence [CI], 0.35 to 0.99) and 0.80 (95% CI, 0.67 to 0.97), respectively. The JAKi group of set 2 showed a significantly higher risk of all-cause mortality (HR, 1.71; 95% CI, 1.32 to 2.20), but the other AEs did not demonstrate increased risks in the JAKi groups.
CONCLUSIONS
In this study, JAKis did not increase the risk of AMI, stroke, CV-related mortality, MACE, VTE, ATE, or cancer in Korean RA patients relative to TNFis.
9.Nailfold capillaroscopy findings of interstitial pneumonia with autoimmune features
Sang-Heon LEE ; Hong Ki MIN ; Se-Hee KIM ; Young Whan KIM ; Kwang Ha YOO ; Hee Joung KIM ; In Ae KIM ; Hae-Rim KIM
The Korean Journal of Internal Medicine 2023;38(6):903-911
Background/Aims:
We evaluated nailfold capillaroscopy (NFC) of interstitial pneumonia with autoimmune features (IPAF) and compared it with that of patients with connective tissue disease-interstitial lung disease (CTD-ILD) and idiopathic interstitial pneumonia (IIP).
Methods:
Patients with newly diagnosed as ILD were evaluated using NFC. Baseline demographic, clinical, serological, and high-resolution CT findings were collected. NFC was semi-quantitatively scored with six domains ranging from 0 to 18. In addition, the overall patterns (sclerodermaon-scleroderma patterns) were determined.
Results:
A total of 81 patients (31 with CTD-ILD, 18 with IPAF, and 32 with IIP) were included. The non-specific interstitial pneumonia pattern was the most common ILD pattern in the CTD-ILD and IPAF groups, whereas the usual interstitial pneumonia pattern was the most common in the IIP group. The semi-quantitative score of the CTD-ILD group was higher than that of the IPAF or IIP groups (5.8 vs 4.2 vs 3.0, p < 0.001, respectively). Giant capillaries and haemorrhages were more frequently present in the CTD-ILD and IPAF groups than in the IIP group. A scleroderma pattern was present in 27.8% of the IPAF group, whereas none of the IIP patients showed a scleroderma pattern.
Conclusions
NFC findings may be useful in classifying patients with ILD into CTD-ILD/IPAF/IIP.
10.A Pilot Genome-Wide Association Study Identifies Novel Markers of Metabolic Syndrome in Patients with Psoriasis
Seung-Min OH ; Su-Kang KIM ; Hye-Jin AHN ; Ki-Heon JEONG
Annals of Dermatology 2023;35(4):285-292
Background:
Recent studies have reported that psoriasis is associated with the development of metabolic syndrome. Genome-wide association studies have been used to discover gene variant markers that occur frequently in case group in relation to specific diseases.
Objective:
The aim of the present study was to investigate the variants of specific genes involved in metabolic syndrome associated with psoriasis.
Methods:
A total of 95 psoriasis patients were recruited and divided into two groups: one with metabolic syndrome (38 patients) and the other without (57 patients). After genotyping, imputation, and quality checking, the association between the several single nucleotide polymorphisms and metabolic syndrome in psoriasis was tested, followed by gene set enrichment analysis.
Results:
We found 76 gene polymorphisms that conferred an increased risk for metabolic syndrome in patients with psoriasis. Four single nucleotide polymorphisms (rs17154774 of FRMD4A, rs77498336 of GPR116, rs75949580 and rs187682251 of MAPK4) showed the strongest association between metabolic syndrome and psoriasis. The epidermal growth factor receptor protein was located at the center of the protein interactions for the gene polymorphisms.
Conclusion
This study identified several previously unknown polymorphisms associated with metabolic syndrome in psoriasis. These results highlight the potential for future genetic studies to elucidate the development, and ultimately prevent the onset, of metabolic syndrome in patients with psoriasis.

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