1.Regenerative Capacity of Alveolar Type 2 Cells Is Proportionally Reduced Following Disease Progression in Idiopathic Pulmonary Fibrosis-Derived Organoid Cultures
Hyeon Kyu CHOI ; Gaeul BANG ; Ju Hye SHIN ; Mi Hwa SHIN ; Ala WOO ; Song Yee KIM ; Sang Hoon LEE ; Eun Young KIM ; Hyo Sup SHIM ; Young Joo SUH ; Ha Eun KIM ; Jin Gu LEE ; Jinwook CHOI ; Ju Hyeon LEE ; Chul Hoon KIM ; Moo Suk PARK
Tuberculosis and Respiratory Diseases 2025;88(1):130-137
Background:
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity.
Methods:
Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells.
Results:
FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells.
Conclusion
This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.
2.Regenerative Capacity of Alveolar Type 2 Cells Is Proportionally Reduced Following Disease Progression in Idiopathic Pulmonary Fibrosis-Derived Organoid Cultures
Hyeon Kyu CHOI ; Gaeul BANG ; Ju Hye SHIN ; Mi Hwa SHIN ; Ala WOO ; Song Yee KIM ; Sang Hoon LEE ; Eun Young KIM ; Hyo Sup SHIM ; Young Joo SUH ; Ha Eun KIM ; Jin Gu LEE ; Jinwook CHOI ; Ju Hyeon LEE ; Chul Hoon KIM ; Moo Suk PARK
Tuberculosis and Respiratory Diseases 2025;88(1):130-137
Background:
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity.
Methods:
Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells.
Results:
FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells.
Conclusion
This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.
3.Regenerative Capacity of Alveolar Type 2 Cells Is Proportionally Reduced Following Disease Progression in Idiopathic Pulmonary Fibrosis-Derived Organoid Cultures
Hyeon Kyu CHOI ; Gaeul BANG ; Ju Hye SHIN ; Mi Hwa SHIN ; Ala WOO ; Song Yee KIM ; Sang Hoon LEE ; Eun Young KIM ; Hyo Sup SHIM ; Young Joo SUH ; Ha Eun KIM ; Jin Gu LEE ; Jinwook CHOI ; Ju Hyeon LEE ; Chul Hoon KIM ; Moo Suk PARK
Tuberculosis and Respiratory Diseases 2025;88(1):130-137
Background:
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity.
Methods:
Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells.
Results:
FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells.
Conclusion
This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.
4.Regenerative Capacity of Alveolar Type 2 Cells Is Proportionally Reduced Following Disease Progression in Idiopathic Pulmonary Fibrosis-Derived Organoid Cultures
Hyeon Kyu CHOI ; Gaeul BANG ; Ju Hye SHIN ; Mi Hwa SHIN ; Ala WOO ; Song Yee KIM ; Sang Hoon LEE ; Eun Young KIM ; Hyo Sup SHIM ; Young Joo SUH ; Ha Eun KIM ; Jin Gu LEE ; Jinwook CHOI ; Ju Hyeon LEE ; Chul Hoon KIM ; Moo Suk PARK
Tuberculosis and Respiratory Diseases 2025;88(1):130-137
Background:
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity.
Methods:
Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells.
Results:
FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells.
Conclusion
This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.
5.Regenerative Capacity of Alveolar Type 2 Cells Is Proportionally Reduced Following Disease Progression in Idiopathic Pulmonary Fibrosis-Derived Organoid Cultures
Hyeon Kyu CHOI ; Gaeul BANG ; Ju Hye SHIN ; Mi Hwa SHIN ; Ala WOO ; Song Yee KIM ; Sang Hoon LEE ; Eun Young KIM ; Hyo Sup SHIM ; Young Joo SUH ; Ha Eun KIM ; Jin Gu LEE ; Jinwook CHOI ; Ju Hyeon LEE ; Chul Hoon KIM ; Moo Suk PARK
Tuberculosis and Respiratory Diseases 2025;88(1):130-137
Background:
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive lung disease that culminates in respiratory failure and death due to irreversible scarring of the distal lung. While initially considered a chronic inflammatory disorder, the aberrant function of the alveolar epithelium is now acknowledged as playing a central role in the pathophysiology of IPF. This study aimed to investigate the regenerative capacity of alveolar type 2 (AT2) cells using IPF-derived alveolar organoids and to examine the effects of disease progression on this capacity.
Methods:
Lung tissues from three pneumothorax patients and six IPF patients (early and advanced stages) were obtained through video-assisted thoracoscopic surgery and lung transplantation. HTII-280+ cells were isolated from CD31-CD45-epithelial cell adhesion molecule (EpCAM)+ cells in the distal lungs of IPF and pneumothorax patients using fluorescence-activated cell sorting (FACS) and resuspended in 48-well plates to establish IPF-derived alveolar organoids. Immunostaining was used to verify the presence of AT2 cells.
Results:
FACS sorting yielded approximately 1% of AT2 cells in early IPF tissue, and the number decreased as the disease progressed, in contrast to 2.7% in pneumothorax. Additionally, the cultured organoids in the IPF groups were smaller and less numerous compared to those from pneumothorax patients. The colony forming efficiency decreased as the disease advanced. Immunostaining results showed that the IPF organoids expressed less surfactant protein C (SFTPC) compared to the pneumothorax group and contained keratin 5+ (KRT5+) cells.
Conclusion
This study confirmed that the regenerative capacity of AT2 cells in IPF decreases as the disease progresses, with IPF-derived AT2 cells inherently exhibiting functional abnormalities and altered differentiation plasticity.
6.The Use of CD44 Variant 9 and Ki-67 Combination Can Predicts Prognosis Better Than Their Single Use in Early Gastric Cancer
Se Il GO ; Gyung Hyuck KO ; Won Sup LEE ; Jeong Hee LEE ; Sang Ho JEONG ; Young Joon LEE ; Soon Chan HONG ; Woo Song HA
Cancer Research and Treatment 2019;51(4):1411-1419
PURPOSE: We previously demonstrated that CD44v9 and Ki-67 played an important role in predicting poor prognosis of early gastric cancer (EGC). However, little is known about combined use of both biomarkers as prognostic biomarker. The present study was performed to investigate the significance of CD44v9 and Ki-67 expression as a combination biomarker for EGC. MATERIALS AND METHODS: With tissue microarray for 158 EGC tissues, we performed immunohistochemical staining for CD44v9 and Ki-67. The whole patients were divided into three groups (group A, CD44v9-negative/Ki-67–low; group B, neither group A or C; and group C, CD44v9-positive/Ki-67–high). Its clinical significance was re-analyzed with adjustment via propensity score matching (PSM). For validation, we performed bootstrap resampling. RESULTS: The median follow-up duration was 90.4 months (range, 3.7 to 120.4 months). In the comparison according to CD44v9/Ki-67 expression, the combined use of the two biomarker clearly separated the three groups by 5-year survival rates (5-YSR, 96.3%, 89.8%, and 76.8% in group A, B, and C, respectively; p=0.009). After PSM, 5-YSR were 97.7% and 76.8% in group A+B and group C, respectively (p=0.002). Multivariable analysis demonstrated that group C had independently poor prognosis (hazard ratio, 9.137; 95% confidence interval, 1.187 to 70.366; p=0.034) compared with group A. Bootstrap resampling internally validated this result (p=0.016). CONCLUSION: This study suggests that both positive CD44v9 and high Ki-67 expression are associated with poor prognosis in EGC, and the combined use of these markers provides better prognostic stratification than the single use of them.
Biomarkers
;
Follow-Up Studies
;
Humans
;
Ki-67 Antigen
;
Prognosis
;
Propensity Score
;
Stomach Neoplasms
;
Survival Rate
7.Screening with the Korean Version of the Mood Disorder Questionnaire for Bipolar Disorders in Adolescents: Korean Validity and Reliability Study.
Se Hoon SHIM ; Jonghun LEE ; Jye Heon SONG ; Beomwoo NAM ; Bo Hyun YOON ; Ha young JIN ; Hyung Mo SUNG ; Jong Hyun JEONG ; Sae Heon JANG ; Duk In JON ; Young Sup WOO ; Won Myong BAHK
Clinical Psychopharmacology and Neuroscience 2018;16(3):316-323
OBJECTIVE: This study aimed to evaluate the validity and reliability of a Korean version of the Mood Disorder Questionnaire-Adolescent version (K-MDQ-A) as a screening instrument for bipolar disorders in adolescents. METHODS: One hundred two adolescents with bipolar disorders and their parents were recruited from November 2014 to November 2016 at 7 training hospitals. One hundred six controls were recruited from each middle school in two cities of South Korea. The parent version of the original MDQ-A was translated into Korean. The parents of all participants completed the K-MDQ-A. The diagnoses of bipolar disorders were determined based on the Korean version of K-SADS-PL. The test-retest reliability with a 10-month interval was investigated in 33 bipolar adolescents. RESULTS: K-MDQ-A yielded a sensitivity of 0.90 and a specificity of 0.92 when using a cut-off score of endorsement of 5 items, indicating that symptoms occurred in the same time period and caused moderate or serious problems. The internal consistency of the K-MDQ-A was good. The correlations between each item and the total score ranged from 0.40 to 0.76 and were all statistically significant. Factor analysis revealed 3 factors that explained 61.25% of the total variance. The mean total score was significantly higher in bipolar adolescents (7.29) than in controls (1.32). The Pearson correlation coefficient for the total test-retest score was 0.59 (p < 0.001). CONCLUSION: The K-MDQ-A completed by parents showed the excellent validity and reliability and may be a useful screening tool for adolescents with bipolar disorders attending in- and outpatient psychiatric clinics.
Adolescent*
;
Bipolar Disorder*
;
Diagnosis
;
Humans
;
Korea
;
Mass Screening*
;
Mood Disorders*
;
Outpatients
;
Parents
;
Reproducibility of Results*
;
Sensitivity and Specificity
8.Diagnostic yield of computed tomography-guided bone biopsy and clinical outcomes of tuberculous and pyogenic spondylitis.
Eun Jeong JOO ; Joon Sup YEOM ; Young Eun HA ; So Yeon PARK ; Chong Suh LEE ; Eun Sang KIM ; Cheol In KANG ; Doo Ryeon CHUNG ; Jae Hoon SONG ; Kyong Ran PECK
The Korean Journal of Internal Medicine 2016;31(4):762-771
BACKGROUND/AIMS: This study aimed to evaluate the efficacy of computed tomography (CT)-guided bone biopsy for the diagnosis of spinal infection and compared the clinical outcomes between tuberculous and pyogenic spinal infections. METHODS: The retrospective cohort study included patients who received CT-guided bone biopsy at a tertiary hospital over the 13 years. RESULTS: Among 100 patients, 67 had pyogenic spondylitis and 33 had tuberculous spondylitis. Pathogens were isolated from bone specimens obtained by CT-guided biopsy in 42 cases, with diagnostic yields of 61% (20/33) for tuberculous spondylitis and 33% (22/67) for pyogenic spondylitis. For 36 culture-proven pyogenic cases, Staphylococcus aureus was the most commonly isolated organism. Patients with pyogenic spondylitis more frequently presented with fever accompanied by an increase in inflammatory markers than did those with tuberculosis. Among all patients who underwent surgery, the incidence of late surgery performed one month after diagnosis was higher in patients with tuberculous infection (56.3%) than in those with pyogenic disease (23.3%, p = 0.026). CONCLUSIONS: Results obtained by CT-guided bone biopsy contributed to prompt diagnoses of spinal infections, especially those caused by tuberculosis. Despite administration of anti-tuberculous agents, patients with tuberculous spondylitis showed an increased tendency to undergo late surgery.
Biopsy*
;
Cohort Studies
;
Diagnosis
;
Fever
;
Humans
;
Incidence
;
Retrospective Studies
;
Spondylitis*
;
Staphylococcus aureus
;
Tertiary Care Centers
;
Tuberculosis
9.CD44 Variant 9 Serves as a Poor Prognostic Marker in Early Gastric Cancer, But Not in Advanced Gastric Cancer.
Se Il GO ; Gyung Hyuck KO ; Won Sup LEE ; Rock Bum KIM ; Jeong Hee LEE ; Sang Ho JEONG ; Young Joon LEE ; Soon Chan HONG ; Woo Song HA
Cancer Research and Treatment 2016;48(1):142-152
PURPOSE: The present study is to investigate the significance of CD44 variant 9 (CD44v9) expression as a biomarker in primary gastric cancer. MATERIALS AND METHODS: With various gastric tissues, we performed immunohistochemical staining for CD44v9. RESULTS: The positive expression rates for CD44v9 in tumor, including adenoma, early gastric cancer (EGC), and advanced gastric cancer (AGC), were higher than those in non-tumor tissues (p=0.003). In addition, the higher expression for CD44v9 was observed as the tissue becomes malignant. In the analysis of 333 gastric cancer tissues, we found that positive expression rates for CD44v9 were higher in the intestinal type or well differentiated gastric cancer than in the diffuse type or poorly differentiated gastric cancer. Interestingly, the positive expression indicated poor prognosis in EGC (5-year survival rate [5-YSR] in stage I, 81.7% vs. 95.2%; p=0.013), but not in AGC (5-YSR in stage II, 66.9% vs. 62.2%; p=0.821; 5-YSR in stage III, 34.5% vs. 32.0%; p=0.929). Moreover, strong positive expression (3+) showed a trend suggesting worse prognosis only in EGC, and it appeared to be associated with lymph node metastasis. CONCLUSION: This study suggests that CD44v9 may be a good biomarker for prognosis prediction and for chemoprevention or biomarker-driven therapies only for EGC.
Adenoma
;
Biological Markers
;
Chemoprevention
;
Lymph Nodes
;
Neoplasm Metastasis
;
Prognosis
;
Stomach Neoplasms*
;
Survival Rate
10.Component-resolved diagnosis using microarray for diagnosing hypersensitivity to raw fruits in birch pollen sensitized children.
Won Bok CHOI ; Jueng Sup YOU ; Yoon Young YI ; Soo In JEONG ; Joon Sup SONG ; Seong YANG ; Il Tae HWANG ; Ha Baik LEE ; Hey Sung BAEK
Allergy, Asthma & Respiratory Disease 2015;3(3):200-205
PURPOSE: Recently, component-resolved diagnosis (CRD) using microarray technology has been introduced to the field of clinical allergy. This study was aimed to investigate the clinical usefulness of microarray-based IgE detection for diagnosing clinical raw fruit allergy in birch pollen-sensitized children. METHODS: Thirty-one children with allergic disease who had been sensitized to pollen were studied. A pollen-sensitized patient was defined as having an allergen-specific history with concomitant positive skin-prick tests (SPTs) to natural allergen extracts or positive allergen-specific IgE. All subjects underwent SPTs for pollen and fruit. In all subjects, specific IgE to pollen and fruit were measured by ImmunoCAP. Specific IgE antibodies to allergen components were determined by a customized allergen microarray (ISAC). RESULTS: Thirteen of the 31 patients (41.9%) had a history of fruit hypersensitivity with positive SPTs. Measuring IgE to allergen components by ISAC, all the 13 patients with fruit hypersensitivity were positive to at least one of Mal d 1, Pru p 1, Pru p 3, Act d 8, and Act d 2 compared to 12 of the 13 patients (92.3%) who had at least 1 positive IgE to fruits (apple, peach, and kiwi) using ImmunoCAP. The sensitivity of ISAC microarray was 100.0% for the diagnosis of fruit hypersensitivity, but its specificity was 27.7% (5/18). The sensitivity of ImmunoCAP was 92.3%, and its specificity was 83.3%. CONCLUSION: The sensitivity of allergen components tested using microarray for the diagnosis of clinical fruit hypersensitivity in children with pollen allergy was high; however, its specificity was low.
Antibodies
;
Betula*
;
Child*
;
Diagnosis*
;
Fruit*
;
Humans
;
Hypersensitivity*
;
Immunoglobulin E
;
Pollen*
;
Prunus persica
;
Rhinitis, Allergic, Seasonal

Result Analysis
Print
Save
E-mail