2.Efficacy of IFN-γ-Primed Umbilical Cord-Derived Mesenchymal Stem Cells on Temporomandibular Joint Osteoarthritis
Hyunjeong KIM ; Yerin KIM ; So-Yeon YUN ; Bu-Kyu LEE
Tissue Engineering and Regenerative Medicine 2024;21(3):473-486
BACKGROUND:
Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease affecting the cartilage and subchondral bone, leading to temporomandibular joint pain and dysfunction. The complex nature of TMJOA warrants effective alternative treatments, and mesenchymal stem cells (MSCs) have shown promise in regenerative therapies. The aim of this study is twofold: firstly, to ascertain the optimal interferon-gamma (IFN-γ)-primed MSC cell line for TMJOA treatment, and secondly, to comprehensively evaluate the therapeutic efficacy of IFN-γ-primed mesenchymal stem cells derived from the human umbilical cord matrix in a rat model of TMJOA.
METHODS:
We analyzed changes in the expression of several key genes associated with OA protection in MSC-secreted compounds. Following this, we performed co-culture experiments using a transwell system to predict gene expression changes in primed MSCs in the TMJOA environment. Subsequently, we investigated the efficacy of the selected IFN-γ-primed human umbilical cord matrix-derived MSCs (hUCM-MSCs) for TMJOA treatment in a rat model.
RESULTS:
IFN-γ-primed MSCs exhibited enhanced expression of IDO, TSG-6, and FGF-2. Moreover, co-culturing with rat OA chondrocytes induced a decrease in pro-inflammatory and extracellular matrix degradation factors. In the rat TMJOA model, IFN-γ-primed MSCs with elevated IDO1, TSG-6, and FGF2 expression exhibited robust anti-inflammatory and therapeutic capacities, promoting the improvement of the inflammatory environment and cartilage regeneration.
CONCLUSION
These findings underscore the importance of prioritizing the mitigation of the inflammatory milieu in TMJOA treatment and highlight IFN-γ-primed MSCs secreting these three factors as a promising, comprehensive therapeutic strategy.
3.Efficacy of pure beta tricalcium phosphate graft in dentoalveolar surgery: a retrospective evaluation based on serial radiographic images
Young‑Jin CHOI ; Hoon‑Je CHANG ; Min Jae KIM ; Jee‑Ho LEE ; Bu‑Kyu LEE
Maxillofacial Plastic and Reconstructive Surgery 2023;45(1):25-
Background:
The use of beta-tricalcium phosphate (beta-TCP) in dental surgery is limited owing to its rapid absorp‑ tion compared to mixed formulations of hydroxyapatite. However, newly developed pure beta-TCP crystals have dem‑ onstrated slow absorption; hence, they last longer within the defect and act as a scaffold until new bone formation.The oral environment is unique and can prove unfavorable for bone grafts due to the high infection rate in the oral cavity and the fragile condition of the oral mucosa. The aim of this study was to evaluate the feasibility of using pure beta-TCP bone grafts in various dental treatments.
Methods:
Panoramic X-ray images of 25 patients who underwent bone grafting during dental surgery were analyzed.A specially treated pure beta-TCP crystal, Neo Bone ® (Neo Bone ® , SN Biologics Co., Ltd, Seoul, Korea), was used in this study. The bone density at the graft site was compared with that of the surrounding bone using the ImageJ software (Wayne Rasband, NIH USA).
Results:
Six months after surgery, the bone graft density was similar to that of the surrounding bone in 20 patients and increased in 5 patients. No adverse effects, such as infection, dehiscence, or graft failure, were observed.
Conclusion
The newly developed pure beta-TCP crystal was slowly absorbed and served as support until new bone formation at the defect site, thus demonstrating its potential for use in various oral conditions requiring bone grafting.
4.Effect of Human Umbilical Cord Matrix-Derived Mesenchymal Stem Cells on Bisphosphonate-Related Osteonecrosis of the Jaw
Gwanghyun YANG ; Young-Nam KIM ; Hyunjeong KIM ; Bu-Kyu LEE
Tissue Engineering and Regenerative Medicine 2021;18(6):975-988
BACKGROUND:
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is a severe sequela caused by bisphosphonates (BPs), which are widely used to treat osteoporosis or other malignancies. However, the mechanism underlying BRONJ remains unclear. Recently, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been studied for treatment of diverse diseases and injuries. This study aimed to investigate the therapeutic effects of hUC-MSCs in BRONJ.
METHODS:
The therapeutic effects of hUC-MSCs were examined in rat bone marrow (rBM)-derived cells using cell viability, colony-forming, and real-time PCR assays and FACS for analyzing essential proinflammatory and bone regeneration markers in vitro. To demonstrate the in vivo therapeutic and adverse effects of transfused hUC-MSCs, microCT, H&E staining, IHC (Angiogenesis marker gene expression) staining, and parathyroid hormone (PTH)/calcium assay were conducted in a BRONJ-induced animal model.
RESULTS:
BP-induced cytotoxicity and inflammation in rBM-derived cells decreased, after co-culture with hUC-MSCs. The expression levels of bone regeneration markers (RUNX2, OSX, and BMP-2) significantly increased in BP-treated rBM-derived cells, after co-culture with hUC-MSCs. The BP-induced abnormal shift in RANKL/OPG expression ratio in rBM-derived cells was normalized by hUC-MSCs. Consistent with these in vitro results, transfused hUC-MSCs markedly decreased BRONJ and significantly healed injured mucosa in the BRONJ-induced animal model. The animals exhibited serious destruction of the kidney structure and increases in serum PTH and calcium levels, which were significantly normalized by hUC-MSC transfusion.
CONCLUSION
hUC-MSCs exerted therapeutic effects on BRONJ in vitro and in vivo through their anti-cytotoxicity, anti-inflammatory activity and ability to recover bone regeneration.
5.An additional lysis procedure during arthrocentesis of the temporomandibular joint
Keon-Mo LEE ; Wan-Hee JANG ; Myoung-Sang YOU ; Bu-Kyu LEE
Maxillofacial Plastic and Reconstructive Surgery 2021;43(1):38-
Background:
Arthrocentesis of the temporomandibular joint (TMJ) is an easy, highly efficient, minimally invasive procedure for treating temporomandibular joint disorders (TMDs). However, in some cases of mouth opening limitation (MOL), routine arthrocentesis is ineffective due to severe fibrotic adhesion in the superior joint space of the TMJ. In this condition, mechanical lysis of the adhesions might be needed to resolve the MOL, as well as other symptoms, such as chronic pain. Currently, this can be achieved by arthroscopic surgery or open TMJ surgery. The objective of this study was to introduce and evaluate our trial of the adhesion lysis procedure during arthrocentesis of the TMJ using normal 18-gauge needles.
Results:
In this study, 40 patients with MOL due to disc derangement underwent conventional arthrocentesis at first and then physical detachment was conducted using the same needle. The change in maximum mouth opening (MMO) and the pain at the TMJ were recorded before, during, and after treatment according to our protocol. The mean increase in MMO after conventional arthrocentesis was 6.6 ± 4.2mm. The mean increase in MMO after the detachment procedure with the same needle was 4.2 ± 2.0 mm. The MMO in ten patients was significantly increased after the detachment procedure than after arthrocentesis alone. In all cases, the pain intensity in the TMJ significantly decreased over time, whereas the MMO increased over time. No adverse effect was observed in all joints during our observation periods.
Conclusion
We confirmed that our simple lysis procedure with the same needle of the arthrocentesis of the TMJ could not only improve the MMO more than after a conventional arthrocentesis but also resolve severe adhesion of the joint space that was ineffective by conventional arthrocentesis. Although this additional lysis procedure is simple, it might reduce the number of cases of more invasive procedures such as arthroscopic surgery or open TMJ surgery.
6.Temporomandibular joint disc plication with MITEK mini anchors: surgical outcome of 65 consecutive joint cases using a minimally invasive approach
Maxillofacial Plastic and Reconstructive Surgery 2020;42(1):14-
Background:
The purpose of this study is to introduce our modified disc plication technique using MITEK mini anchors and to evaluate the clinical outcome for patients with internal derangement (ID) of the temporomandibular joint (TMJ).
Patients and methods:
We evaluated 65 joints in 46 patients, comprised 32 women and 14 men, who first visited the Asan Medical Center from December 2012 to December 2016. The age of the patients ranged from 14 to 79 years, with a mean age of 36.6 years. The patients presented with joint problems including pain, joint noise, and mouth opening limitation (MOL). Patients who met our inclusion criteria underwent unilateral or bilateral disc repositioning surgery with our minimally invasive disc plication technique using MITEK mini anchors and No. 2-0 Ethibond® braided polyester sutures. The variables taken into account in this study were the range of maximum mouth opening (MMO), painful symptoms (evaluated with the visual analog scale, VAS), and the type of noise (click, popping, crepitus) in the TMJ.
Results:
Preoperative examination revealed painful symptoms in 50.7% (n = 35) of the operated joints (n = 69) and the presence of clicks in 56.5% (n = 39). Postoperative examination revealed that 4.3% (n = 3) of the operated joints had painful symptoms with lower intensity than that in the preoperative condition. Additionally, 17.4% (n = 12) had residual noise in the TMJ, among which two were clicking and the other 10 had mild crepitus. The intensity of the postoperative residual noise was significantly decreased in all cases compared to that in the preoperative condition. Among patients with MOL below 38mm (n = 18), the mean MMO was 31.4mm preoperatively and 44.2mm at 6 months postoperatively, with a mean increase of 13.8 mm. A barely visible scar at the operation site was noted during the postoperative observation period, with no significant complications such as facial palsy or permanent occlusal disharmony.
Conclusion
Subjective symptoms in all patients improved following the surgery. TMJ disc plication using MITEK mini anchors with our minimally invasive approach may be a feasible and effective surgical option for treating TMJ ID patients who are not responsive to conservative treatment.
7.A Case of Hemophagocytic Lymphohistiocytosis Presenting with Neck Mass in a Child
Bu Kwan KIL ; Dong Won LEE ; Jeong Kyu KIM
Korean Journal of Head and Neck Oncology 2020;36(2):55-59
Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening one syndrome of excessive immune activation. This immune dysregulation disorder is prominently associated with cytopenias and combinations of clinical signs and extreme inflammation symptoms. For survival, it is important to diagnose early and treat appropriately. We report a case of 10 years old boy who was admitted to the hospital with a month history of fever and cervical lymph node enlargement. There were signs of hemophagocytic histiocytosis in the lymph node and bone marrow. The etiology, diagnosis, and treatment of hemophagocytic lymphohistiocytosis are reviewed.
8.Association of maxillary dental developmental abnormality with precocious puberty: a case-control study
Yesel KIM ; Nam-Ki LEE ; Jae Hyun KIM ; Jeong-Kui KU ; Bu-Kyu LEE ; Hoi-In JUNG ; Sun-Kyu CHOI
Maxillofacial Plastic and Reconstructive Surgery 2020;42(1):30-
Background:
Dental studies of precocious puberty have focused on examination of jaw and dentition growth. The aim of the study was to analyze the relationship between precocious puberty and maxillary dental developmental abnormalities (DDAs).
Methods:
This retrospective study was conducted on the Korean patients in whom dental panoramic and hand-wrist radiographs had been taken before they were 15 years of age. The maxillary DDAs were assessed as mesiodens, congenital missing teeth, peg-shape lateral incisors, or impacted teeth. The chronological ages of the control group members were within the normal range of the hand-wrist bone age. Others with a peak luteinizing hormone of ≥ 5 and < 5 IU/L were allocated to central precocious puberty (CPP) and peripheral precocious puberty (PPP), respectively.
Results:
Of the enrolled 270 patients, 195, 52, and 23 were allocated to the control, CPP, and PPP groups, respectively. The maxillary DDAs were significantly more prevalent in the CPP group than in the other groups. Among those with maxillary DDA, the mesiodens predominated. Age- and sex-adjusted multivariate analysis revealed maxillary DDA (odds ratio, 3.36; 95% CI, 1.60-7.05) and especially mesiodens (odds ratio, 5.52; CI, 2.29-13.28) to be significantly associated with CPP.
Conclusions
Maxillary DDAs were significantly more prevalent in the CPP group than in the PPP or control groups. Among the many types of maxillary DDAs, mesiodens was significantly associated with CPP and may be considered a predictor of the development of CPP.
9.Association of maxillary dental developmental abnormality with precocious puberty: a case-control study
Yesel KIM ; Nam-Ki LEE ; Jae Hyun KIM ; Jeong-Kui KU ; Bu-Kyu LEE ; Hoi-In JUNG ; Sun-Kyu CHOI
Maxillofacial Plastic and Reconstructive Surgery 2020;42(1):30-
Background:
Dental studies of precocious puberty have focused on examination of jaw and dentition growth. The aim of the study was to analyze the relationship between precocious puberty and maxillary dental developmental abnormalities (DDAs).
Methods:
This retrospective study was conducted on the Korean patients in whom dental panoramic and hand-wrist radiographs had been taken before they were 15 years of age. The maxillary DDAs were assessed as mesiodens, congenital missing teeth, peg-shape lateral incisors, or impacted teeth. The chronological ages of the control group members were within the normal range of the hand-wrist bone age. Others with a peak luteinizing hormone of ≥ 5 and < 5 IU/L were allocated to central precocious puberty (CPP) and peripheral precocious puberty (PPP), respectively.
Results:
Of the enrolled 270 patients, 195, 52, and 23 were allocated to the control, CPP, and PPP groups, respectively. The maxillary DDAs were significantly more prevalent in the CPP group than in the other groups. Among those with maxillary DDA, the mesiodens predominated. Age- and sex-adjusted multivariate analysis revealed maxillary DDA (odds ratio, 3.36; 95% CI, 1.60-7.05) and especially mesiodens (odds ratio, 5.52; CI, 2.29-13.28) to be significantly associated with CPP.
Conclusions
Maxillary DDAs were significantly more prevalent in the CPP group than in the PPP or control groups. Among the many types of maxillary DDAs, mesiodens was significantly associated with CPP and may be considered a predictor of the development of CPP.
10.A Case of Hemophagocytic Lymphohistiocytosis Presenting with Neck Mass in a Child
Bu Kwan KIL ; Dong Won LEE ; Jeong Kyu KIM
Korean Journal of Head and Neck Oncology 2020;36(2):55-59
Hemophagocytic lymphohistiocytosis (HLH) is a rare but life-threatening one syndrome of excessive immune activation. This immune dysregulation disorder is prominently associated with cytopenias and combinations of clinical signs and extreme inflammation symptoms. For survival, it is important to diagnose early and treat appropriately. We report a case of 10 years old boy who was admitted to the hospital with a month history of fever and cervical lymph node enlargement. There were signs of hemophagocytic histiocytosis in the lymph node and bone marrow. The etiology, diagnosis, and treatment of hemophagocytic lymphohistiocytosis are reviewed.

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