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Cell cultures are an important part of the research and treatment of autoimmune connective tissue diseases. By culturing the various cell types involved in autoimmune connective tissue diseases (ACTDs), researchers are able to broaden the knowledge about these diseases that, in the near future, may lead to finding cures. Fibroblast cultures and chondrocyte cultures allow scientists to study the behavior, physiology and intracellular interactions of these cells.
ACTD | Affected Tissue | Type of Cell Culture | Involved Immune Elements | Immunopathogenesis |
---|---|---|---|---|
Dermatomyositis (DM) | Muscles, skin [4]. | 2D and 3D fibroblast cultures and skin models. | Myositis-specific antibodies: nuclear matrix protein 2 (anti-NXP-2), transcriptional intermediary factor 1 γ (anti-TIF1-γ), melanoma differentiation-associated protein 5 (anti-MDA-5), small ubiquitin-like modifier activating enzyme 1 (anti-SAE-1), subunit of nucleosome remodeling deacetylase complex (anti-Mi-2) [4]. | Characterized by a chronic inflammatory process affecting the skin and muscles. Infiltration of the affected tissues by immune elements leads to tissue damage and inflammation. Also associated with microangiopathy in affected tissues, which contributes to skin changes, muscle weakness and other clinical features [4]. |
Juvenile idiopathic arthritis (JIA) | Joints, cartilage, bones [5]. | 2D and 3D fibroblast and chondrocyte cultures. | Macrophages and T lymphocytes [5]. | Overactive immune response, characterized by an influx of T cells and macrophages into the synovium and the release of proinflammatory cytokines, which promotes inflammation and tissue damage in the joints. Various subtypes with significant differences in pathogenesis [5]. |
Lupus erythematosus (LE) | Various, including joints, blood cells, brain, heart, skin, kidneys, lungs [6]. | 2D and 3D fibroblast, chondrocyte and cardiomyocyte cultures, peripheral blood mononuclear cells (PBMC) cultures, skin models. | Defective autoantibodies recruiting T and B lymphocytes [6]. | Dysregulated immune response, leading to the activation of various components of the immune system. Imbalance between proinflammatory and regulatory immune responses. Production of autoantibodies which target and attack the body’s own tissues. Formation of immune complexes by antibodies with their target antigens, complexes can deposit in various tissues leading to inflammation and tissue damage [6]. |
Mixed connective tissue disease (MCTD) | Various, including skin, muscles, small capillary vessels, lungs, kidneys [7]. | 2D and 3D fibroblast, chondrocyte and endothelial cell cultures, PBMC cultures. | Anti-U1-RNP antibodies [7]. | Immunological imbalance features similar and overlapping with lupus, systemic sclerosis and polymyositis [7]. |
Polymyositis (PM) | Muscles [8]. | 2D and 3D fibroblast and myocyte cultures. | CD8+ T cells [8]. | Infiltration of CD8+ T cells into the muscle tissue, which recognize and attack muscle fibers, leading to muscle inflammation and damage. Persistent inflammation interferes with the muscle regeneration processes. As muscle fibers are damaged and replaced by fibrous tissue, muscle strength and function are compromised [8]. |
Rheumatoid arthritis (RA) | Joints, cartilage and bones [9]. | 2D and 3D fibroblast and chondrocyte cultures. | CD4+ T helper cells, rheumatoid factor (RF), anti–citrullinated protein antibodies (ACPA) [9]. | Dysregulation of immune response with activation of CD4+ T helper cells and production of proinflammatory cytokines. Synthesis of RF and ACPA autoantibodies, leading to inflammation and tissue damage, mostly in joint areas. Formation and deposition of immune complexes in tissue which contribute to inflammation. Cytokine-stimulated bone erosion and deformation caused by osteoclasts [9]. |
Spondyloarthropathies | Joints of the vertebral column [10]. | 2D and 3D fibroblast and chondrocyte cultures. | Human leukocyte antigen B27 (HLA-B27) antibodies [10]. | Inappropriate immune response, characterized by the activation of immune cells, leading to chronic inflammation and infiltration of the affected joints, including the spine and peripheral joints. Overproduction of proinflammatory cytokines contributing to enthesitis and tissue damage. Various subtypes with significant differences in pathogenesis [10]. |
Systemic sclerosis (SSc) | Skin, soft tissue organs, blood vessels, joints [11]. | 2D and 3D fibroblast, PBMC, mesenchymal stem cell (MSC) and endothelial cell cultures, skin models. | T cells, CD4+ T cells [11]. | Persistent activation of fibroblasts, leading to imbalance in extra cellular matrix (ECM) production and degradation processes resulting in fibrosis. Activation of endothelial cells leads to an abnormal release of vasoactive factors, resulting in blood flow changes and vessel dysfunction. Infiltration of the affected tissues by inflammatory cells and release of proinflammatory cytokines and chemokines result in tissue damage [11]. |
Vasculitis | Various blood vessels [12]. | 2D and 3D endothelial cell cultures, PBMC cultures. | Anti-neutrophil cytoplasmic antibodies (ANCAs) [12]. | Dysregulation of the immune system, leading to the activation of immune cells and production of proinflammatory cytokines and chemokines resulting in damage to vessels. Activation of endothelial cells, resulting in the promotion of immune cell infiltration. Various subtypes with significant differences in pathogenesis [12]. |
Medium Name | Composition | Application |
---|---|---|
Dulbecco’s Modified Eagle Medium (DMEM) | Glucose, amino acids, vitamins, minerals and a buffering agent to maintain a constant pH. Available in numerous modifications, including increased glucose concentration, sodium pyruvate addition or prolonged shelf life [15]. | A wide range of cell types, including fibroblasts, epithelial cells, smooth muscle cells, neurons, glial cells and certain cell lines [15]. |
Ham’s F-12 | Modification of Eagle Medium similar in composition to DMEM but with a higher concentration of bicarbonate, which helps to regulate the pH of the medium and maintain proper osmotic pressure [15]. | A wide range of cell types, including epithelial cells, fibroblasts, neurons, endothelial cells, hepatocytes, adipocytes and cells that are sensitive to changes in osmotic pressure [15]. |
M199 | Modification of Eagle Medium similar in composition to DMEM but with high concentration of inorganic salts, which help to maintain the proper osmotic pressure and provide a stable environment for the cells [16]. | Fibroblasts, endothelial cells, epithelial cells, hybridoma cells, hepatocytes, smooth muscle cells and cells sensitive to osmotic pressure changes [16]. |
α-Modified Eagle Medium (α-MEM) | A modification of the original minimum essential medium (MEM) with high concentration of vitamins and low concentration of pyruvate [16]. | Fibroblasts, epithelial cells, stem cells, hybridoma cells, adipocytes and osteoblasts [16]. |
Roswell Park Memorial Institute (RPMI) 1640 | A modification of MEM supplemented with additional compounds, including HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), which helps to maintain the pH of the medium in the presence of carbon dioxide and sodium bicarbonate, which helps to buffer the medium [15]. | Lymphocytes, cancer cells, hybridoma cells, adipocytes, fibroblasts and epithelial cells [15]. |
Human Endothelial Serum Free Medium (Human Endothelial SFM) | Serum-free medium with a range of supplements, including growth factors, amino acids, vitamins and trace elements that are essential for EC growth, such as Vascular Endothelial Growth Factor (VEGF), Basic Fibroblast Growth Factor (bFGF) and Epidermal Growth Factor (EGF) [17]. | Human ECs, such as human umbilical vein endothelial cells (HUVECs), human dermal microvascular endothelial cells (HDMECs), human pulmonary microvascular endothelial cells (HPMECs) and human coronary artery endothelial cells (HCAECs) [17]. |
Endothelial Cell Growth Medium (EGM) | Variety of nutrients, growth factors and supplements that are necessary for the growth and survival of ECs, which can include growth factors such as VEGF, bFGF and EGF, as well as other components, such as hydrocortisone, ascorbic acid and heparin [18]. | It is important to note that EGM medium is formulated for specific types of ECs. Therefore, different ECs will require different EGMs. Some of the cells that can be cultured in this medium are HUVECs, human microvascular endothelial cells (HMVECs), human pulmonary artery endothelial cells (HPAECs), HDMECs, HCAECs and human retinal microvascular endothelial cells (HRMECs) [18]. |