1.Regenerative Functions of Regulatory T Cells and Current Strategies Utilizing Mesenchymal Stem Cells in Immunomodulatory Tissue Regeneration
Jinsung AHN ; Bowon KIM ; Alvin Bacero BELLO ; James J. MOON ; Yoshie ARAI ; Soo-Hong LEE
Tissue Engineering and Regenerative Medicine 2025;22(2):167-180
		                        		
		                        			 BACKGROUND:
		                        			Regulatory T cells (Tregs) are essential for maintaining immune homeostasis and facilitating tissue regeneration by fostering an environment conducive to tissue repair. However, in damaged tissues, excessive inflammatory responses can overwhelm the immunomodulatory capacity of Tregs, compromising their functionality and potentially hindering effective regeneration. Mesenchymal stem cells (MSCs) play a key role in enhancing Treg function. MSCs enhance Treg activity through indirect interactions, such as cytokine secretion, and direct interactions via membrane proteins. 
		                        		
		                        			METHODS:
		                        			This review examines the regenerative functions of Tregs across various tissues, including bone, cartilage, muscle, and skin, and explores strategies to enhance Treg functionality using MSCs. Advanced techniques, such as the overexpression of relevant genes in MSCs, are highlighted for their potential to further enhance Treg function. Additionally, emerging technologies utilizing extracellular vesicles (EVs) and cell membrane-derived vesicles derived from MSCs offer promising alternatives to circumvent the potential side effects associated with live cell therapies. This review proposes approaches to enhance Treg function and promote tissue regeneration and also outlines future research directions. 
		                        		
		                        			RESULTS
		                        			AND CONCLUSION: This review elucidates recent technological advancements aimed at enhancing Treg function using MSCs and examines their potential to improve tissue regeneration efficiency. 
		                        		
		                        		
		                        		
		                        	
2.Regenerative Functions of Regulatory T Cells and Current Strategies Utilizing Mesenchymal Stem Cells in Immunomodulatory Tissue Regeneration
Jinsung AHN ; Bowon KIM ; Alvin Bacero BELLO ; James J. MOON ; Yoshie ARAI ; Soo-Hong LEE
Tissue Engineering and Regenerative Medicine 2025;22(2):167-180
		                        		
		                        			 BACKGROUND:
		                        			Regulatory T cells (Tregs) are essential for maintaining immune homeostasis and facilitating tissue regeneration by fostering an environment conducive to tissue repair. However, in damaged tissues, excessive inflammatory responses can overwhelm the immunomodulatory capacity of Tregs, compromising their functionality and potentially hindering effective regeneration. Mesenchymal stem cells (MSCs) play a key role in enhancing Treg function. MSCs enhance Treg activity through indirect interactions, such as cytokine secretion, and direct interactions via membrane proteins. 
		                        		
		                        			METHODS:
		                        			This review examines the regenerative functions of Tregs across various tissues, including bone, cartilage, muscle, and skin, and explores strategies to enhance Treg functionality using MSCs. Advanced techniques, such as the overexpression of relevant genes in MSCs, are highlighted for their potential to further enhance Treg function. Additionally, emerging technologies utilizing extracellular vesicles (EVs) and cell membrane-derived vesicles derived from MSCs offer promising alternatives to circumvent the potential side effects associated with live cell therapies. This review proposes approaches to enhance Treg function and promote tissue regeneration and also outlines future research directions. 
		                        		
		                        			RESULTS
		                        			AND CONCLUSION: This review elucidates recent technological advancements aimed at enhancing Treg function using MSCs and examines their potential to improve tissue regeneration efficiency. 
		                        		
		                        		
		                        		
		                        	
3.Regenerative Functions of Regulatory T Cells and Current Strategies Utilizing Mesenchymal Stem Cells in Immunomodulatory Tissue Regeneration
Jinsung AHN ; Bowon KIM ; Alvin Bacero BELLO ; James J. MOON ; Yoshie ARAI ; Soo-Hong LEE
Tissue Engineering and Regenerative Medicine 2025;22(2):167-180
		                        		
		                        			 BACKGROUND:
		                        			Regulatory T cells (Tregs) are essential for maintaining immune homeostasis and facilitating tissue regeneration by fostering an environment conducive to tissue repair. However, in damaged tissues, excessive inflammatory responses can overwhelm the immunomodulatory capacity of Tregs, compromising their functionality and potentially hindering effective regeneration. Mesenchymal stem cells (MSCs) play a key role in enhancing Treg function. MSCs enhance Treg activity through indirect interactions, such as cytokine secretion, and direct interactions via membrane proteins. 
		                        		
		                        			METHODS:
		                        			This review examines the regenerative functions of Tregs across various tissues, including bone, cartilage, muscle, and skin, and explores strategies to enhance Treg functionality using MSCs. Advanced techniques, such as the overexpression of relevant genes in MSCs, are highlighted for their potential to further enhance Treg function. Additionally, emerging technologies utilizing extracellular vesicles (EVs) and cell membrane-derived vesicles derived from MSCs offer promising alternatives to circumvent the potential side effects associated with live cell therapies. This review proposes approaches to enhance Treg function and promote tissue regeneration and also outlines future research directions. 
		                        		
		                        			RESULTS
		                        			AND CONCLUSION: This review elucidates recent technological advancements aimed at enhancing Treg function using MSCs and examines their potential to improve tissue regeneration efficiency. 
		                        		
		                        		
		                        		
		                        	
4.Regenerative Functions of Regulatory T Cells and Current Strategies Utilizing Mesenchymal Stem Cells in Immunomodulatory Tissue Regeneration
Jinsung AHN ; Bowon KIM ; Alvin Bacero BELLO ; James J. MOON ; Yoshie ARAI ; Soo-Hong LEE
Tissue Engineering and Regenerative Medicine 2025;22(2):167-180
		                        		
		                        			 BACKGROUND:
		                        			Regulatory T cells (Tregs) are essential for maintaining immune homeostasis and facilitating tissue regeneration by fostering an environment conducive to tissue repair. However, in damaged tissues, excessive inflammatory responses can overwhelm the immunomodulatory capacity of Tregs, compromising their functionality and potentially hindering effective regeneration. Mesenchymal stem cells (MSCs) play a key role in enhancing Treg function. MSCs enhance Treg activity through indirect interactions, such as cytokine secretion, and direct interactions via membrane proteins. 
		                        		
		                        			METHODS:
		                        			This review examines the regenerative functions of Tregs across various tissues, including bone, cartilage, muscle, and skin, and explores strategies to enhance Treg functionality using MSCs. Advanced techniques, such as the overexpression of relevant genes in MSCs, are highlighted for their potential to further enhance Treg function. Additionally, emerging technologies utilizing extracellular vesicles (EVs) and cell membrane-derived vesicles derived from MSCs offer promising alternatives to circumvent the potential side effects associated with live cell therapies. This review proposes approaches to enhance Treg function and promote tissue regeneration and also outlines future research directions. 
		                        		
		                        			RESULTS
		                        			AND CONCLUSION: This review elucidates recent technological advancements aimed at enhancing Treg function using MSCs and examines their potential to improve tissue regeneration efficiency. 
		                        		
		                        		
		                        		
		                        	
5.Regenerative Functions of Regulatory T Cells and Current Strategies Utilizing Mesenchymal Stem Cells in Immunomodulatory Tissue Regeneration
Jinsung AHN ; Bowon KIM ; Alvin Bacero BELLO ; James J. MOON ; Yoshie ARAI ; Soo-Hong LEE
Tissue Engineering and Regenerative Medicine 2025;22(2):167-180
		                        		
		                        			 BACKGROUND:
		                        			Regulatory T cells (Tregs) are essential for maintaining immune homeostasis and facilitating tissue regeneration by fostering an environment conducive to tissue repair. However, in damaged tissues, excessive inflammatory responses can overwhelm the immunomodulatory capacity of Tregs, compromising their functionality and potentially hindering effective regeneration. Mesenchymal stem cells (MSCs) play a key role in enhancing Treg function. MSCs enhance Treg activity through indirect interactions, such as cytokine secretion, and direct interactions via membrane proteins. 
		                        		
		                        			METHODS:
		                        			This review examines the regenerative functions of Tregs across various tissues, including bone, cartilage, muscle, and skin, and explores strategies to enhance Treg functionality using MSCs. Advanced techniques, such as the overexpression of relevant genes in MSCs, are highlighted for their potential to further enhance Treg function. Additionally, emerging technologies utilizing extracellular vesicles (EVs) and cell membrane-derived vesicles derived from MSCs offer promising alternatives to circumvent the potential side effects associated with live cell therapies. This review proposes approaches to enhance Treg function and promote tissue regeneration and also outlines future research directions. 
		                        		
		                        			RESULTS
		                        			AND CONCLUSION: This review elucidates recent technological advancements aimed at enhancing Treg function using MSCs and examines their potential to improve tissue regeneration efficiency. 
		                        		
		                        		
		                        		
		                        	
6.Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial)
Bo Seong YUN ; Kwang-Beom LEE ; Keun Ho LEE ; Ha Kyun CHANG ; Joo-Young KIM ; Myong Cheol LIM ; Chel Hun CHOI ; Hanbyoul CHO ; Dae-Yeon KIM ; Yun Hwan KIM ; Joong Sub CHOI ; Chae Hyeong LEE ; Jae-Weon KIM ; Sang Wun KIM ; Yong Bae KIM ; Chi-Heum CHO ; Dae Gy HONG ; Yong Jung SONG ; Seob JEON ; Min Kyu KIM ; Dae Hoon JEONG ; Hyun PARK ; Seok Mo KIM ; Sang-Il PARK ; Jae-Yun SONG ; Asima MUKHOPADHYAY ; Dang Huy Quoc THINH ; Nirmala Chandralega KAMPAN ; Grace J. LEE ; Jae-Hoon KIM ; Keun-Yong EOM ; Ju-Won ROH
Journal of Gynecologic Oncology 2024;35(5):e57-
		                        		
		                        			 Background:
		                        			Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. 
		                        		
		                        			Methods
		                        			The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. 
		                        		
		                        		
		                        		
		                        	
7.Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial)
Bo Seong YUN ; Kwang-Beom LEE ; Keun Ho LEE ; Ha Kyun CHANG ; Joo-Young KIM ; Myong Cheol LIM ; Chel Hun CHOI ; Hanbyoul CHO ; Dae-Yeon KIM ; Yun Hwan KIM ; Joong Sub CHOI ; Chae Hyeong LEE ; Jae-Weon KIM ; Sang Wun KIM ; Yong Bae KIM ; Chi-Heum CHO ; Dae Gy HONG ; Yong Jung SONG ; Seob JEON ; Min Kyu KIM ; Dae Hoon JEONG ; Hyun PARK ; Seok Mo KIM ; Sang-Il PARK ; Jae-Yun SONG ; Asima MUKHOPADHYAY ; Dang Huy Quoc THINH ; Nirmala Chandralega KAMPAN ; Grace J. LEE ; Jae-Hoon KIM ; Keun-Yong EOM ; Ju-Won ROH
Journal of Gynecologic Oncology 2024;35(5):e57-
		                        		
		                        			 Background:
		                        			Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. 
		                        		
		                        			Methods
		                        			The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. 
		                        		
		                        		
		                        		
		                        	
8.Therapeutic effects of surgical debulking of metastatic lymph nodes in cervical cancer IIICr: a trial protocol for a phase III, multicenter, randomized controlled study (KGOG1047/DEBULK trial)
Bo Seong YUN ; Kwang-Beom LEE ; Keun Ho LEE ; Ha Kyun CHANG ; Joo-Young KIM ; Myong Cheol LIM ; Chel Hun CHOI ; Hanbyoul CHO ; Dae-Yeon KIM ; Yun Hwan KIM ; Joong Sub CHOI ; Chae Hyeong LEE ; Jae-Weon KIM ; Sang Wun KIM ; Yong Bae KIM ; Chi-Heum CHO ; Dae Gy HONG ; Yong Jung SONG ; Seob JEON ; Min Kyu KIM ; Dae Hoon JEONG ; Hyun PARK ; Seok Mo KIM ; Sang-Il PARK ; Jae-Yun SONG ; Asima MUKHOPADHYAY ; Dang Huy Quoc THINH ; Nirmala Chandralega KAMPAN ; Grace J. LEE ; Jae-Hoon KIM ; Keun-Yong EOM ; Ju-Won ROH
Journal of Gynecologic Oncology 2024;35(5):e57-
		                        		
		                        			 Background:
		                        			Bulky or multiple lymph node (LN) metastases are associated with poor prognosis in cervical cancer, and the size or number of LN metastases is not yet reflected in the staging system and therapeutic strategy. Although the therapeutic effects of surgical resection of bulky LNs before standard treatment have been reported in several retrospective studies, wellplanned randomized clinical studies are lacking. Therefore, the aim of the Korean Gynecologic Oncology Group (KGOG) 1047/DEBULK trial is to investigate whether the debulking surgery of bulky or multiple LNs prior to concurrent chemoradiation therapy (CCRT) improves the survival rate of patients with cervical cancer IIICr diagnosed by imaging tests. 
		                        		
		                        			Methods
		                        			The KGOG 1047/DEBULK trial is a phase III, multicenter, randomized clinical trial involving patients with bulky or multiple LN metastases in cervical cancer IIICr. This study will include patients with a short-axis diameter of a pelvic or para-aortic LN ≥2 cm or ≥3 LNs with a short-axis diameter ≥1 cm and for whom CCRT is planned. The treatment arms will be randomly allocated in a 1:1 ratio to either receive CCRT (control arm) or undergo surgical debulking of bulky or multiple LNs before CCRT (experimental arm). CCRT consists of extended-field external beam radiotherapy/pelvic radiotherapy, brachytherapy and LN boost, and weekly chemotherapy with cisplatin (40 mg/m 2 ), 4–6 times administered intravenously.The primary endpoint will be 3-year progression-free survival rate. The secondary endpoints will be 3-year overall survival rate, treatment-related complications, and accuracy of radiological diagnosis of bulky or multiple LNs. 
		                        		
		                        		
		                        		
		                        	
9.Evaluation of the Efficacy and Safety of DW1903 in Patients with Gastritis: A Randomized, Double-Blind, Noninferiority, Multicenter, Phase 3 study
Jie-Hyun KIM ; Hwoon-Yong JUNG ; In Kyung YOO ; Seon-Young PARK ; Jae Gyu KIM ; Jae Kyu SUNG ; Jin Seok JANG ; Gab Jin CHEON ; Kyoung Oh KIM ; Tae Oh KIM ; Soo Teik LEE ; Kwang Bum CHO ; Hoon Jai CHUN ; Jong-Jae PARK ; Moo In PARK ; Jae-Young JANG ; Seong Woo JEON ; Jin Woong CHO ; Dae Hwan KANG ; Gwang Ha KIM ; Jae J. KIM ; Sang Gyun KIM ; Nayoung KIM ; Yong Chan LEE ; Su Jin HONG ; Hyun-Soo KIM ; Sora LEE ; Sang Woo LEE
Gut and Liver 2024;18(1):70-76
		                        		
		                        			 Background/Aims:
		                        			H2 receptor antagonists (H2RA) have been used to treat gastritis by inhibiting gastric acid. Proton pump inhibitors (PPIs) are more potent acid suppressants than H2RA.However, the efficacy and safety of low-dose PPI for treating gastritis remain unclear. The aim was to investigate the efficacy and safety of low-dose PPI for treating gastritis. 
		                        		
		                        			Methods:
		                        			A double-blind, noninferiority, multicenter, phase 3 clinical trial randomly assigned 476 patients with endoscopic erosive gastritis to a group using esomeprazole 10 mg (DW1903) daily and a group using famotidine 20 mg (DW1903R1) daily for 2 weeks. The full-analysis set included 319 patients (DW1903, n=159; DW1903R1, n=160) and the per-protocol set included 298 patients (DW1903, n=147; DW1903R1, n=151). The primary endpoint (erosion improvement rate) and secondary endpoint (erosion and edema cure rates, improvement rates of hemorrhage, erythema, and symptoms) were assessed after the treatment. Adverse events were compared. 
		                        		
		                        			Results:
		                        			According to the full-analysis set, the erosion improvement rates in the DW1903 and DW1903R1 groups were 59.8% and 58.8%, respectively. According to the per-protocol analysis, the erosion improvement rates in the DW1903 and DW1903R1 groups were 61.9% and 59.6%, respectively. Secondary endpoints were not significantly different between two groups except that the hemorrhagic improvement rate was higher in DW1903 with statistical tendency. The number of adverse events were not statistically different. 
		                        		
		                        			Conclusions
		                        			DW1903 of a low-dose PPI was not inferior to DW1903R1 of H2RA. Thus, lowdose PPI can be a novel option for treating gastritis (ClinicalTrials.gov Identifier: NCT05163756). 
		                        		
		                        		
		                        		
		                        	
10.Can we omit systematic biopsies in patients undergoing MRI fusion-targeted prostate biopsies?
Jeffrey J LEOW ; Soon Hock KOH ; Marcus Wl CHOW ; Wayren LOKE ; Rolando SALADA ; Seok Kwan HONG ; Yuyi YEOW ; Chau Hung LEE ; Cher Heng TAN ; Teck Wei TAN
Asian Journal of Andrology 2023;25(1):43-49
		                        		
		                        			
		                        			Magnetic resonance imaging (MRI)-targeted prostate biopsy is the recommended investigation in men with suspicious lesion(s) on MRI. The role of concurrent systematic in addition to targeted biopsies is currently unclear. Using our prospectively maintained database, we identified men with at least one Prostate Imaging-Reporting and Data System (PI-RADS) ≥3 lesion who underwent targeted and/or systematic biopsies from May 2016 to May 2020. Clinically significant prostate cancer (csPCa) was defined as any Gleason grade group ≥2 cancer. Of 545 patients who underwent MRI fusion-targeted biopsy, 222 (40.7%) were biopsy naïve, 247 (45.3%) had previous prostate biopsy(s), and 76 (13.9%) had known prostate cancer undergoing active surveillance. Prostate cancer was more commonly found in biopsy-naïve men (63.5%) and those on active surveillance (68.4%) compared to those who had previous biopsies (35.2%; both P < 0.001). Systematic biopsies provided an incremental 10.4% detection of csPCa among biopsy-naïve patients, versus an incremental 2.4% among those who had prior negative biopsies. Multivariable regression found age (odds ratio [OR] = 1.03, P = 0.03), prostate-specific antigen (PSA) density ≥0.15 ng ml-2 (OR = 3.24, P < 0.001), prostate health index (PHI) ≥35 (OR = 2.43, P = 0.006), higher PI-RADS score (vs PI-RADS 3; OR = 4.59 for PI-RADS 4, and OR = 9.91 for PI-RADS 5; both P < 0.001) and target lesion volume-to-prostate volume ratio ≥0.10 (OR = 5.26, P = 0.013) were significantly associated with csPCa detection on targeted biopsy. In conclusion, for men undergoing MRI fusion-targeted prostate biopsies, systematic biopsies should not be omitted given its incremental value to targeted biopsies alone. The factors such as PSA density ≥0.15 ng ml-2, PHI ≥35, higher PI-RADS score, and target lesion volume-to-prostate volume ratio ≥0.10 can help identify men at higher risk of csPCa.
		                        		
		                        		
		                        		
		                        			Male
		                        			;
		                        		
		                        			Humans
		                        			;
		                        		
		                        			Prostate/pathology*
		                        			;
		                        		
		                        			Prostatic Neoplasms/pathology*
		                        			;
		                        		
		                        			Prostate-Specific Antigen
		                        			;
		                        		
		                        			Magnetic Resonance Imaging/methods*
		                        			;
		                        		
		                        			Image-Guided Biopsy/methods*
		                        			;
		                        		
		                        			Retrospective Studies
		                        			
		                        		
		                        	
            
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