1.Current Stem Cell Therapy for Osteoarthritis
Yoojun NAM ; Yeri Alice RIM ; Ji Hyeon JU
Korean Journal of Medicine 2019;94(2):145-151
Osteoarthritis is a musculoskeletal disease representative of an aging society. As medical conditions are usually complicated in an aging population, osteoarthritis becomes more frequently encountered in the physician's office. There is a growing need, therefore, for physicians to pay attention to this common orthopedic condition. Cartilage degeneration, arthritic pain, and joint dysfunction are major manifestations of osteoarthritis, and degenerated cartilage is difficult to repair with conventional treatment modalities. Scientists and physicians have developed various therapeutic strategies, including the use of stem cells. Here, we discuss previous and current progress in cartilage regenerative therapy against osteoarthritis.
Adult Stem Cells
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Aging
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Cartilage
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Chondrogenesis
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Induced Pluripotent Stem Cells
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Joints
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Musculoskeletal Diseases
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Orthopedics
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Osteoarthritis
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Physicians' Offices
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Stem Cells
2.Current Stem Cell Therapy for Osteoarthritis
Yoojun NAM ; Yeri Alice RIM ; Ji Hyeon JU
Korean Journal of Medicine 2019;94(2):145-151
Osteoarthritis is a musculoskeletal disease representative of an aging society. As medical conditions are usually complicated in an aging population, osteoarthritis becomes more frequently encountered in the physician's office. There is a growing need, therefore, for physicians to pay attention to this common orthopedic condition. Cartilage degeneration, arthritic pain, and joint dysfunction are major manifestations of osteoarthritis, and degenerated cartilage is difficult to repair with conventional treatment modalities. Scientists and physicians have developed various therapeutic strategies, including the use of stem cells. Here, we discuss previous and current progress in cartilage regenerative therapy against osteoarthritis.
3.Guidelines for Manufacturing and Application of Organoids: Skin
Seunghee LEE ; Yeri Alice RIM ; Juryun KIM ; Su Hyon LEE ; Hye Jung PARK ; Hyounwoo KIM ; Sun-Ju AHN ; Ji Hyeon JU
International Journal of Stem Cells 2024;17(2):182-193
To address the limitations of animal testing, scientific research is increasingly focused on developing alternative testing methods. These alternative tests utilize cells or tissues derived from animals or humans for in vitro testing, as well as artificial tissues and organoids. In western countries, animal testing for cosmetics has been banned, leading to the adoption of artificial skin for toxicity evaluation, such as skin corrosion and irritation assessments. Standard guidelines for skin organoid technology becomes necessary to ensure consistent data and evaluation in replacing animal testing with in vitro methods. These guidelines encompass aspects such as cell sourcing, culture techniques, quality requirements and assessment, storage and preservation, and organoid-based assays.
4.Sodium Chloride Aggravates Arthritis via Th17 Polarization.
Seung Min JUNG ; Youngkyun KIM ; Juryun KIM ; Hyerin JUNG ; Hyoju YI ; Yeri Alice RIM ; Narae PARK ; Seung Ki KWOK ; Sung Hwan PARK ; Ji Hyeon JU
Yonsei Medical Journal 2019;60(1):88-97
PURPOSE: Sodium chloride (NaCl) has been proposed as a driving factor in autoimmune diseases through the induction of pathogenic CD4+ T helper cells that produce interleukin-17 (Th17 cells). This study investigated the effects of NaCl on inflammatory arthritis in mice and humans. MATERIALS AND METHODS: Collagen-induced arthritis (CIA) mice were fed a normal or high-salt diet ad libitum, and clinical and histologic features of arthritis were evaluated. The proportion of Th17 cells in the spleens of CIA mice fed a normal or high-salt diet was evaluated by flow cytometry, and the expression of IL-17 in joints and intestines was determined by immunohistochemical staining. We also analyzed the effect of NaCl on Th17 differentiation from peripheral blood monocytes of patients with rheumatoid arthritis (RA) and osteoarthritis (OA) and evaluated the contents of sodium and IL-17 in the synovial fluid of RA and OA patients. RESULTS: NaCl increased murine and human Th17 cell differentiation in a dose-dependent manner. Clinical and histological arthritis was more severe in the high-salt-fed CIA mice, compared to control CIA mice. The proportion of Th17 cells among splenocytes was higher in CIA mice fed a high-salt diet. Expression of synovial and intestinal IL-17 was also higher in high-salt-fed CIA mice. Comparison of synovial fluid between RA patients and OA patients revealed that Na+ and IL-17 were more abundant in RA synovial fluid. CONCLUSION: This study suggests that NaCl can aggravate arthritis by affecting Th17 differentiation. Accordingly, limiting salt intake may be helpful for treating inflammatory arthritis, such as RA.
Animals
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Arthritis*
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Arthritis, Experimental
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Arthritis, Rheumatoid
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Autoimmune Diseases
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Diet
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Flow Cytometry
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Humans
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Interleukin-17
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Intestines
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Joints
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Mice
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Monocytes
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Osteoarthritis
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Sodium Chloride*
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Sodium*
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Spleen
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Synovial Fluid
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T-Lymphocytes, Helper-Inducer
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Th17 Cells
5.Lupus Heart Disease Modeling with Combination of Induced Pluripotent Stem Cell-Derived Cardiomyocytes and Lupus Patient Serum
Narae PARK ; Yeri Alice RIM ; Hyerin JUNG ; Yoojun NAM ; Ji Hyeon JU
International Journal of Stem Cells 2022;15(3):233-246
Background and Objectives:
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease mainly affecting young women of childbearing age. SLE affects the skin, joints, muscles, kidneys, lungs, and heart. Cardiovascular complications are common causes of death in patients with SLE. However, the complexity of the cardiovascular system and the rarity of SLE make it difficult to investigate these morbidities. Patient-derived induced pluripotent stem cells (iPSCs) serve as a novel tool for drug screening and pathophysiological studies in the absence of patient samples.
Methods:
and Results: We differentiated CMs from HC- and SLE-iPSCs using 2D culture platforms. SLE-CMs showed decreased proliferation and increased levels of fibrosis and hypertrophy marker expression; however, HC-and SLE-monolayer CMs reacted differently to SLE serum treatment. HC-iPSCs were also differentiated into CMs using 3D spheroid culture and anti-Ro autoantibody was treated along with SLE serum. 3D-HC-CMs generated more mature CMs compared to the CMs generated using 2D culture. The treatment of anti-Ro autoantibody rapidly increased the gene expression of fibrosis, hypertrophy, and apoptosis markers, and altered the calcium signaling in the CMs.
Conclusions
iPSC derived cardiomyocytes with patient-derived serum, and anti-Ro antibody treatment could serve in effective autoimmune disease modeling including SLE. We believe that the present study might briefly provide possibilities on the application of a combination of patient-derived materials and iPSCs in disease modeling of autoimmune diseases.
6.Eupatilin Ameliorates Collagen Induced Arthritis.
Juryun KIM ; Youngkyun KIM ; Hyoju YI ; Hyerin JUNG ; Yeri Alice RIM ; Narae PARK ; Seung Min JUNG ; Sung Hwan PARK ; Ji Hyeon JU
Journal of Korean Medical Science 2015;30(3):233-239
Eupatilin is the main active component of DA-9601, an extract from Artemisia. Recently, eupatilin was reported to have anti-inflammatory properties. We investigated the anti-arthritic effect of eupatilin in a murine arthritis model and human rheumatoid synoviocytes. DA-9601 was injected into collagen-induced arthritis (CIA) mice. Arthritis score was regularly evaluated. Mouse monocytes were differentiated into osteoclasts when eupatilin was added simultaneously. Osteoclasts were stained with tartrate-resistant acid phosphatase and then manually counted. Rheumatoid synoviocytes were stimulated with TNF-alpha and then treated with eupatilin, and the levels of IL-6 and IL-1beta mRNA expression in synoviocytes were measured by RT-PCR. Intraperitoneal injection of DA-9601 reduced arthritis scores in CIA mice. TNF-alpha treatment of synoviocytes increased the expression of IL-6 and IL-1beta mRNAs, which was inhibited by eupatilin. Eupatilin decreased the number of osteoclasts in a concentration dependent manner. These findings, showing that eupatilin and DA-9601 inhibited the expression of inflammatory cytokines and the differentiation of osteoclasts, suggest that eupatilin and DA-9601 is a candidate anti-inflammatory agent.
Animals
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Anti-Inflammatory Agents/pharmacology/*therapeutic use
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Arthritis, Experimental/chemically induced/*drug therapy
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Arthritis, Rheumatoid/drug therapy/pathology
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Cell Differentiation/*drug effects
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Cells, Cultured
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Collagen Type II
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Cytokines/biosynthesis
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Disease Models, Animal
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Drugs, Chinese Herbal/therapeutic use
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Female
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Flavonoids/pharmacology/*therapeutic use
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Humans
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Inflammation/drug therapy/immunology
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Interleukin-1beta/genetics/metabolism
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Interleukin-6/genetics/metabolism
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Lymph Nodes/cytology
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Mice
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Mice, Inbred DBA
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Monocytes/cytology
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Osteoclasts/*cytology
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Plant Extracts/pharmacology
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RNA, Messenger/biosynthesis
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Synovial Membrane/cytology
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T-Lymphocytes, Regulatory/cytology/immunology
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Tumor Necrosis Factor-alpha/pharmacology
7.Interrupting oral infection of Porphyromonas gingivalis with anti-FimA antibody attenuates bacterial dissemination to the arthritic joint and improves experimental arthritis
Sang Hoon JEONG ; Yoojun NAM ; Hyerin JUNG ; Juryun KIM ; Yeri Alice RIM ; Narae PARK ; Kijun LEE ; Seungjin CHOI ; Yeonsue JANG ; Yena KIM ; Ji Hoi MOON ; Seung Min JUNG ; Sung Hwan PARK ; Ji Hyeon JU
Experimental & Molecular Medicine 2018;50(3):e460-
Rheumatoid arthritis (RA) is a chronic autoimmune disease that typically results in strong inflammation and bone destruction in the joints. It is generally known that the pathogenesis of RA is linked to cardiovascular and periodontal diseases. Though rheumatoid arthritis and periodontitis share many pathologic features such as a perpetual inflammation and bone destruction, the precise mechanism underlying a link between these two diseases has not been fully elucidated. Collagen-induced arthritis (CIA) mice were orally infected with Porphyromonas gingivalis (Pg) or Pg preincubated with an anti-FimA antibody (FimA Ab) specific for fimbriae that are flexible appendages on the cell surface. Pg-infected CIA mice showed oral microbiota disruption and increased alveolar bone loss and had synovitis and joint bone destruction. However, preincubation with FimA Ab led to a significant reduction in the severity of both oral disease and arthritis. Moreover, FimA Ab attenuated bacterial attachment and aggregation on human gingival and rheumatoid arthritis synovial fibroblasts. In addition, we discovered bacteria may utilize dendritic cells, macrophages and neutrophils to migrate into the joints of CIA mice. These results suggest that disrupting Pg fimbriae function by FimA Ab ameliorates RA.