1.Effects of Late-Passage Small Umbilical Cord–Derived Fast Proliferating Cells on Tenocytes from Degenerative Rotator Cuff Tears under an Interleukin 1β-Induced Tendinopathic Environment
Ah-Young LEE ; Ju-Young PARK ; Sam Joongwon HWANG ; Kwi-Hoon JANG ; Chris Hyunchul JO
Tissue Engineering and Regenerative Medicine 2024;21(8):1217-1231
BACKGROUND:
Tendinopathy is a chronic tendon disease. Mesenchymal stem cells (MSCs), known for their antiinflammatory properties, may lose effectiveness with extensive culturing. Previous research introduced ‘‘small umbilical cord–derived fast proliferating cells’’ (smumf cells), isolated using a novel minimal cube explant method. These cells maintained their MSC characteristics through long-term culture. Thus, the purpose of the present study was to assess the anti-inflammatory effects of late-passage smumf cells at P10 on tenocytes derived from degenerative rotator cuff tears in a tendinopathic environment.
METHODS:
The mRNA expression with respect to aging of MSCs and secretion of growth factors (GFs) by smumf cells at P10 were measured. mRNA and protein synthesis in tenocytes with respect to the tenocyte phenotype, inflammatory cytokines, and matrix- degradation enzymes were measured. The inflammatory signal pathways involving nuclear factor kappa B (NF-jB) and mitogen-activated protein kinase (MAPK) in tenocytes were also investigated. The proliferative response of degenerative tenocytes to co-culture with smumf cells over 7 days in varying IL-1β induced tendinopathic environments was investigated.
RESULTS
smumf cells at P10 showed no signs of aging compared to those at P3. smumf cells at P10, secreting 2,043 pg/ ml of hepatocyte growth factor (HGF), showed a 1.88-fold (p = .002) increase in HGF secretion in a tendinopathic environment. Degenerative tenocytes co-cultured with smumf cells showed significantly increased protein expression levels of collagen type I (Col I) and the Col I/III ratio by 1.46-fold (p < .001) and 1.66-fold (p < .001), respectively. The smumf cells at P10 reduced both mRNA and protein expression levels of matrix metalloproteinases-1, -2, -3, -8, -9, and -13 in tenocytes and attenuated NF-jB (phosphorylated IjBa/IjBa and phosphorylated p65/p65) and MAPK (phosphorylated p38/p38 and phosphorylated JNK/JNK) pathways activated by IL-1β. Removal of IL-1β from the co-culture accelerated the growth of tenocytes by 1.42-fold (p < .001). Removal of IL-1β accelerated tenocyte growth in co-cultures.CONCULSION Late-passage smumf cells exert anti-inflammatory effects on tenocytes derived from degenerative rotator cuff tears under a tendinopathic environment, primarily through the secretion of growth factors (GFs).
2.Effects of Late-Passage Small Umbilical Cord–Derived Fast Proliferating Cells on Tenocytes from Degenerative Rotator Cuff Tears under an Interleukin 1β-Induced Tendinopathic Environment
Ah-Young LEE ; Ju-Young PARK ; Sam Joongwon HWANG ; Kwi-Hoon JANG ; Chris Hyunchul JO
Tissue Engineering and Regenerative Medicine 2024;21(8):1217-1231
BACKGROUND:
Tendinopathy is a chronic tendon disease. Mesenchymal stem cells (MSCs), known for their antiinflammatory properties, may lose effectiveness with extensive culturing. Previous research introduced ‘‘small umbilical cord–derived fast proliferating cells’’ (smumf cells), isolated using a novel minimal cube explant method. These cells maintained their MSC characteristics through long-term culture. Thus, the purpose of the present study was to assess the anti-inflammatory effects of late-passage smumf cells at P10 on tenocytes derived from degenerative rotator cuff tears in a tendinopathic environment.
METHODS:
The mRNA expression with respect to aging of MSCs and secretion of growth factors (GFs) by smumf cells at P10 were measured. mRNA and protein synthesis in tenocytes with respect to the tenocyte phenotype, inflammatory cytokines, and matrix- degradation enzymes were measured. The inflammatory signal pathways involving nuclear factor kappa B (NF-jB) and mitogen-activated protein kinase (MAPK) in tenocytes were also investigated. The proliferative response of degenerative tenocytes to co-culture with smumf cells over 7 days in varying IL-1β induced tendinopathic environments was investigated.
RESULTS
smumf cells at P10 showed no signs of aging compared to those at P3. smumf cells at P10, secreting 2,043 pg/ ml of hepatocyte growth factor (HGF), showed a 1.88-fold (p = .002) increase in HGF secretion in a tendinopathic environment. Degenerative tenocytes co-cultured with smumf cells showed significantly increased protein expression levels of collagen type I (Col I) and the Col I/III ratio by 1.46-fold (p < .001) and 1.66-fold (p < .001), respectively. The smumf cells at P10 reduced both mRNA and protein expression levels of matrix metalloproteinases-1, -2, -3, -8, -9, and -13 in tenocytes and attenuated NF-jB (phosphorylated IjBa/IjBa and phosphorylated p65/p65) and MAPK (phosphorylated p38/p38 and phosphorylated JNK/JNK) pathways activated by IL-1β. Removal of IL-1β from the co-culture accelerated the growth of tenocytes by 1.42-fold (p < .001). Removal of IL-1β accelerated tenocyte growth in co-cultures.CONCULSION Late-passage smumf cells exert anti-inflammatory effects on tenocytes derived from degenerative rotator cuff tears under a tendinopathic environment, primarily through the secretion of growth factors (GFs).
3.Effects of Late-Passage Small Umbilical Cord–Derived Fast Proliferating Cells on Tenocytes from Degenerative Rotator Cuff Tears under an Interleukin 1β-Induced Tendinopathic Environment
Ah-Young LEE ; Ju-Young PARK ; Sam Joongwon HWANG ; Kwi-Hoon JANG ; Chris Hyunchul JO
Tissue Engineering and Regenerative Medicine 2024;21(8):1217-1231
BACKGROUND:
Tendinopathy is a chronic tendon disease. Mesenchymal stem cells (MSCs), known for their antiinflammatory properties, may lose effectiveness with extensive culturing. Previous research introduced ‘‘small umbilical cord–derived fast proliferating cells’’ (smumf cells), isolated using a novel minimal cube explant method. These cells maintained their MSC characteristics through long-term culture. Thus, the purpose of the present study was to assess the anti-inflammatory effects of late-passage smumf cells at P10 on tenocytes derived from degenerative rotator cuff tears in a tendinopathic environment.
METHODS:
The mRNA expression with respect to aging of MSCs and secretion of growth factors (GFs) by smumf cells at P10 were measured. mRNA and protein synthesis in tenocytes with respect to the tenocyte phenotype, inflammatory cytokines, and matrix- degradation enzymes were measured. The inflammatory signal pathways involving nuclear factor kappa B (NF-jB) and mitogen-activated protein kinase (MAPK) in tenocytes were also investigated. The proliferative response of degenerative tenocytes to co-culture with smumf cells over 7 days in varying IL-1β induced tendinopathic environments was investigated.
RESULTS
smumf cells at P10 showed no signs of aging compared to those at P3. smumf cells at P10, secreting 2,043 pg/ ml of hepatocyte growth factor (HGF), showed a 1.88-fold (p = .002) increase in HGF secretion in a tendinopathic environment. Degenerative tenocytes co-cultured with smumf cells showed significantly increased protein expression levels of collagen type I (Col I) and the Col I/III ratio by 1.46-fold (p < .001) and 1.66-fold (p < .001), respectively. The smumf cells at P10 reduced both mRNA and protein expression levels of matrix metalloproteinases-1, -2, -3, -8, -9, and -13 in tenocytes and attenuated NF-jB (phosphorylated IjBa/IjBa and phosphorylated p65/p65) and MAPK (phosphorylated p38/p38 and phosphorylated JNK/JNK) pathways activated by IL-1β. Removal of IL-1β from the co-culture accelerated the growth of tenocytes by 1.42-fold (p < .001). Removal of IL-1β accelerated tenocyte growth in co-cultures.CONCULSION Late-passage smumf cells exert anti-inflammatory effects on tenocytes derived from degenerative rotator cuff tears under a tendinopathic environment, primarily through the secretion of growth factors (GFs).
4.Effects of Late-Passage Small Umbilical Cord–Derived Fast Proliferating Cells on Tenocytes from Degenerative Rotator Cuff Tears under an Interleukin 1β-Induced Tendinopathic Environment
Ah-Young LEE ; Ju-Young PARK ; Sam Joongwon HWANG ; Kwi-Hoon JANG ; Chris Hyunchul JO
Tissue Engineering and Regenerative Medicine 2024;21(8):1217-1231
BACKGROUND:
Tendinopathy is a chronic tendon disease. Mesenchymal stem cells (MSCs), known for their antiinflammatory properties, may lose effectiveness with extensive culturing. Previous research introduced ‘‘small umbilical cord–derived fast proliferating cells’’ (smumf cells), isolated using a novel minimal cube explant method. These cells maintained their MSC characteristics through long-term culture. Thus, the purpose of the present study was to assess the anti-inflammatory effects of late-passage smumf cells at P10 on tenocytes derived from degenerative rotator cuff tears in a tendinopathic environment.
METHODS:
The mRNA expression with respect to aging of MSCs and secretion of growth factors (GFs) by smumf cells at P10 were measured. mRNA and protein synthesis in tenocytes with respect to the tenocyte phenotype, inflammatory cytokines, and matrix- degradation enzymes were measured. The inflammatory signal pathways involving nuclear factor kappa B (NF-jB) and mitogen-activated protein kinase (MAPK) in tenocytes were also investigated. The proliferative response of degenerative tenocytes to co-culture with smumf cells over 7 days in varying IL-1β induced tendinopathic environments was investigated.
RESULTS
smumf cells at P10 showed no signs of aging compared to those at P3. smumf cells at P10, secreting 2,043 pg/ ml of hepatocyte growth factor (HGF), showed a 1.88-fold (p = .002) increase in HGF secretion in a tendinopathic environment. Degenerative tenocytes co-cultured with smumf cells showed significantly increased protein expression levels of collagen type I (Col I) and the Col I/III ratio by 1.46-fold (p < .001) and 1.66-fold (p < .001), respectively. The smumf cells at P10 reduced both mRNA and protein expression levels of matrix metalloproteinases-1, -2, -3, -8, -9, and -13 in tenocytes and attenuated NF-jB (phosphorylated IjBa/IjBa and phosphorylated p65/p65) and MAPK (phosphorylated p38/p38 and phosphorylated JNK/JNK) pathways activated by IL-1β. Removal of IL-1β from the co-culture accelerated the growth of tenocytes by 1.42-fold (p < .001). Removal of IL-1β accelerated tenocyte growth in co-cultures.CONCULSION Late-passage smumf cells exert anti-inflammatory effects on tenocytes derived from degenerative rotator cuff tears under a tendinopathic environment, primarily through the secretion of growth factors (GFs).
5.Effects of Late-Passage Small Umbilical Cord–Derived Fast Proliferating Cells on Tenocytes from Degenerative Rotator Cuff Tears under an Interleukin 1β-Induced Tendinopathic Environment
Ah-Young LEE ; Ju-Young PARK ; Sam Joongwon HWANG ; Kwi-Hoon JANG ; Chris Hyunchul JO
Tissue Engineering and Regenerative Medicine 2024;21(8):1217-1231
BACKGROUND:
Tendinopathy is a chronic tendon disease. Mesenchymal stem cells (MSCs), known for their antiinflammatory properties, may lose effectiveness with extensive culturing. Previous research introduced ‘‘small umbilical cord–derived fast proliferating cells’’ (smumf cells), isolated using a novel minimal cube explant method. These cells maintained their MSC characteristics through long-term culture. Thus, the purpose of the present study was to assess the anti-inflammatory effects of late-passage smumf cells at P10 on tenocytes derived from degenerative rotator cuff tears in a tendinopathic environment.
METHODS:
The mRNA expression with respect to aging of MSCs and secretion of growth factors (GFs) by smumf cells at P10 were measured. mRNA and protein synthesis in tenocytes with respect to the tenocyte phenotype, inflammatory cytokines, and matrix- degradation enzymes were measured. The inflammatory signal pathways involving nuclear factor kappa B (NF-jB) and mitogen-activated protein kinase (MAPK) in tenocytes were also investigated. The proliferative response of degenerative tenocytes to co-culture with smumf cells over 7 days in varying IL-1β induced tendinopathic environments was investigated.
RESULTS
smumf cells at P10 showed no signs of aging compared to those at P3. smumf cells at P10, secreting 2,043 pg/ ml of hepatocyte growth factor (HGF), showed a 1.88-fold (p = .002) increase in HGF secretion in a tendinopathic environment. Degenerative tenocytes co-cultured with smumf cells showed significantly increased protein expression levels of collagen type I (Col I) and the Col I/III ratio by 1.46-fold (p < .001) and 1.66-fold (p < .001), respectively. The smumf cells at P10 reduced both mRNA and protein expression levels of matrix metalloproteinases-1, -2, -3, -8, -9, and -13 in tenocytes and attenuated NF-jB (phosphorylated IjBa/IjBa and phosphorylated p65/p65) and MAPK (phosphorylated p38/p38 and phosphorylated JNK/JNK) pathways activated by IL-1β. Removal of IL-1β from the co-culture accelerated the growth of tenocytes by 1.42-fold (p < .001). Removal of IL-1β accelerated tenocyte growth in co-cultures.CONCULSION Late-passage smumf cells exert anti-inflammatory effects on tenocytes derived from degenerative rotator cuff tears under a tendinopathic environment, primarily through the secretion of growth factors (GFs).
6.Effect of platelet-rich plasma in Achilles tendon allograft in rabbits
Seok-Hong PARK ; Dong-Yub KIM ; Won-Jae LEE ; Min JANG ; Seong Mok JEONG ; Sae-Kwang KU ; Young-Sam KWON ; Sungho YUN
Journal of Veterinary Science 2024;25(2):e22-
Background:
Achilles tendon is composed of dense connective tissue and is one of the largest tendons in the body. In veterinary medicine, acute ruptures are associated with impact injury or sharp trauma. Healing of the ruptured tendon is challenging because of poor blood and nerve supply as well as the residual cell population. Platelet-rich plasma (PRP) contains numerous bioactive agents and growth factors and has been utilized to promote healing in bone, soft tissue, and tendons.
Objective:
The purpose of this study was to evaluate the healing effect of PRP injected into the surrounding fascia of the Achilles tendon after allograft in rabbits.
Methods:
Donor rabbits (n = 8) were anesthetized and 16 lateral gastrocnemius tendons were fully transected bilaterally. Transected tendons were decellularized and stored at −80°C prior to allograft. The allograft was placed on the partially transected medial gastrocnemius tendon in the left hindlimb of 16 rabbits. The allograft PRP group (n = 8) had 0.3 mL of PRP administered in the tendon and the allograft control group (n = 8) did not receive any treatment. After 8 weeks, rabbits were euthanatized and allograft tendons were transected for macroscopic, biomechanical, and histological assessment.
Results:
The allograft PRP group exhibited superior macroscopic assessment scores, greater tensile strength, and a histologically enhanced healing process compared to those in the allograft control group.
Conclusions
Our results suggest administration of PRP on an allograft tendon has a positive effect on the healing process in a ruptured Achilles tendon.
7.Epigenetic Regulation of the Expression of T Cell Stimulatory and Inhibitory Factors by Histone H3 Lysine Modification Enzymes and Its Prognostic Roles in Glioblastoma
Sang Hyuk LEE ; Seung Hwan KIM ; Taek Min NAM ; Ji Hwan JANG ; Kyu Hong KIM ; Young-Sam LEE ; Minseok S. KIM ; Mee-Seon KIM ; Sung Yup JIN ; Moonok LEE ; Sung-Hun LEE ; Young Zoon KIM
Journal of Korean Medical Science 2023;38(33):e258-
Background:
This study aimed to identify the specific T cell co-stimulatory and co-inhibitory factors that play prognostic roles in patients with glioblastoma. Additionally, the unique histone H3 modification enzymes that regulate the expression levels of these specific costimulatory and co-inhibitory factors were investigated.
Methods:
The medical records of 84 patients newly diagnosed with glioblastoma at our institution from January 2006 to December 2020 were retrospectively reviewed.Immunohistochemical (IHC) staining for T cell co-stimulatory factors (CD27, CD28, CD137, OX40, and ICOS), T cell co-inhibitory factors (CTLA4, PD1, PD-L1, TIM3, and CD200R), and histone H3 lysine modification enzymes (MLL4, RIZ, EZH1, NSD2, KDM5c, JMJD1a, UTX, and JMJD5) was performed on archived paraffin-embedded tissues obtained by biopsy or resection. Quantitative real time-polymerase chain reaction (qRT-PCR) was performed for specific factors, which demonstrated causal relationships, in order to validate the findings of the IHC examinations.
Results:
The mean follow-up duration was 27.5 months (range, 4.1–43.5 months). During this period, 76 patients (90.5%) died, and the mean OS was 19.4 months (95% confidence interval, 16.3–20.9 months). Linear positive correlations were observed between the expression levels of CD28 and JMJD1a (R2 linear = 0.982) and those of CD137 and UTX (R2 linear = 1.528). Alternatively, significant negative correlations were observed between the expression levels of CTLA4 and RIZ (R2 linear = −1.746) and those of PD-L1 and EZH1 (R2 linear = −2.118); relationships were confirmed by qRT-PCR. In the multivariate analysis, increased expression levels of CD28 (P = 0.042), and CD137 (P = 0.009), and decreased expression levels of CTLA4 (P = 0.003), PD-L1 (P = 0.020), and EZH1 (P = 0.040) were significantly associated with longer survival.
Conclusion
These findings suggest that the expression of certain T cell co-stimulatory factors, such as CD28 and CD 137, and co-inhibitory factors, such as CTLA4 and PD-L1 are associated with prognosis of glioblastoma patients.
8.Low-Dose Three-Dimensional Rotational Angiography for Evaluating Intracranial Aneurysms: Analysis of Image Quality and Radiation Dose
Hee Jong KI ; Bum-soo KIM ; Jun-Ki KIM ; Jai Ho CHOI ; Yong Sam SHIN ; Yangsean CHOI ; Na-Young SHIN ; Jinhee JANG ; Kook-jin AHN
Korean Journal of Radiology 2022;23(2):256-263
Objective:
This study aimed to evaluate the image quality and dose reduction of low-dose three-dimensional (3D) rotational angiography (RA) for evaluating intracranial aneurysms.
Materials and Methods:
We retrospectively evaluated the clinical data and 3D RA datasets obtained from 146 prospectively registered patients (male:female, 46:100; median age, 58 years; range, 19–81 years). The subjective image quality of 79 examinations obtained from a conventional method and 67 examinations obtained from a low-dose (5-seconds and 0.10-μGy/frame) method was assessed by two neurointerventionists using a 3-point scale for four evaluation criteria. The total image quality score was then obtained as the average of the four scores. The image quality scores were compared between the two methods using a noninferiority statistical testing, with a margin of -0.2 (i.e., score of low-dose group – score of conventional group). For the evaluation of dose reduction, dose-area product (DAP) and air kerma (AK) were analyzed and compared between the two groups.
Results:
The mean total image quality score ± standard deviation of the 3D RA was 2.97 ± 0.17 by reader 1 and 2.95 ± 0.20 by reader 2 for conventional group and 2.92 ± 0.30 and 2.95 ± 0.22, respectively, for low-dose group. The image quality of the 3D RA in the low-dose group was not inferior to that of the conventional group according to the total image quality score as well as individual scores for the four criteria in both readers. The mean DAP and AK per rotation were 5.87 Gy-cm2 and 0.56 Gy, respectively, in the conventional group, and 1.32 Gy-cm2 (p < 0.001) and 0.17 Gy (p < 0.001), respectively, in the low-dose group.
Conclusion
Low-dose 3D RA was not inferior in image quality and reduced the radiation dose by 70%–77% compared to the conventional 3D RA in evaluating intracranial aneurysms.
9.Clinical features and management of snake bites in 70 dogs in Korea
Dongseok KIM ; Seonghoon KIM ; Jin-Kyung KIM ; Jae Hyun LIM ; Geonho CHOI ; Seulgi BAE ; Young-Sam KWON ; Min JANG
Journal of Veterinary Science 2022;23(6):e81-
Background:
Snakebites remain a devastating and life-threatening environmental hazard.While the management of snakebites has been well described in humans, few clinical data and guidelines exist for dogs, especially in Korea.
Objectives:
This retrospective study evaluated the clinical features of 70 dogs with snakebite wounds in Korea.
Methods:
The medical records of 72 dogs that presented to three animal hospitals from June 2008 to July 2021 were reviewed; among these, 70 dogs that met the inclusion criteria were enrolled. Their signalment, history, clinical signs, physical examination, blood analysis, treatment, and prognosis were also evaluated.
Results:
Of 70 dog owners, 35 (50%) witnessed the bite, with a mean time between bite and hospital presentation of 9.7 ± 4.1 h in 58 dogs. Blood smears were evaluated in 45 dogs, of which 28 (62%) showed echinocytosis. Anemia and acute kidney injury were found in 21 (29%) and 2 dogs (3%), respectively. A total of 37 dogs (53%) were hospitalized, 5 (7%) of which died.
Conclusions
The most significant finding was the high prevalence of echinocytosis. The data from this retrospective study could inform the management of dogs bitten by snakes in Korea.
10.Pilot study for the Psychometric Validation of the Sheffield Profile for Assessment and Referral to Care (SPARC) in Korean Cancer Patients
Jung Hye KWON ; Sun Kyung BAEK ; Do Yeun KIM ; Yu Jung KIM ; Myung Ah LEE ; Hye Jin CHOI ; Ja Min BYUN ; Jin Young JEONG ; Sam H AHMEDZAI ; Geun-Doo JANG
Cancer Research and Treatment 2021;53(1):25-31
Purpose:
This study aimed to validate the Sheffield Profile for Assessment and Referral to Care (SPARC) as an effective tool for screening palliative care needs among Korean cancer patients.
Materials and Methods:
The English version of the SPARC was translated by four Korean oncologists and reconciled by a Korean language specialist and a medical oncologist fluent in English. After the first version of the Korean SPARC (K-SPARC) was developed, back-translation into English was performed by a professional translator and bilingual oncologist. The back-translated version was reviewed by the original author (S.H.A.), and modifications were made (ver. 2). The second version of the K-SPARC was tested against other questionnaires, including the Functional Assessment of Cancer Therapy-General (FACT-G) and the Edmonton Symptom Assessment System (ESAS).
Results:
Thirty patients were enrolled in the pilot trial. Fifteen were male, and the median age was 64.5 years. Six patients had an Eastern Cooperative Oncology Group performance status of 2 or more. All patients except one were receiving chemotherapy. Regarding internal consistency, the Cronbach’s α scores for physical symptoms, psychological issues, religious and spiritual issues, independency and activity, family and social issues, and treatment issues were 0.812, 0.804, 0.589, 0.843, 0.754, and 0.822, respectively. The correlation coefficients between the SPARC and FACT-G were 0.479 (p=0.007) for the physical domain and –0.130 (p=0.493) for the social domain.
Conclusion
This pilot study indicates that the K-SPARC could be a reliable tool to screen for palliative care needs among Korean cancer patients. A further study to validate our findings is ongoing.

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