Assessment of mesenchymal stem/stromal cell-based therapy in K/BxN serum transfer-induced arthritis.
Frontiers in immunology
Rheumatoid arthritis (RA) is an autoimmune disease characterized by synovial hyperplasia and cartilage/bone destruction with systemic comorbidities. Despite advances in understanding the aetiology of RA and novel biologic drugs, a substantial number of individuals with RA remain intolerant or resistant to these therapies. In this context, mesenchymal stem/stromal cell (MSC)-based therapy has emerged as an innovative therapeutic alternative to address unresolved treatment issues for patients with RA thanks to the immunomodulatory properties of these cells. The majority of preclinical studies in MSC-based therapy have been conducted using the well-known collagen-induced arthritis (CIA) mouse model however due to its low incidence, the mouse strain restriction and the prolonged induction phase of collagen-induced arthritis, alternative experimental models of RA have been developed such as K/BxN serum transfer-induced arthritis (STIA), which mimics many of human RA features. In this study, we evaluate whether the K/BxN STIA model could be used as an alternative model to study the immunomodulatory potential of MSC-based therapy. Unexpectedly, our data suggest that adipose-derived MSC-based therapy is unsuitable for modulating the progression of K/BxN serum-transfer arthritis in mice despite the various experimental parameters tested. Based on the differences in the immune status and monocytic/macrophage balance among the different arthritic models, these results could help to identify the cellular targets of the MSCs and, most importantly to predict the RA patients that will respond positively to MSC-based therapy.
10.3389/fimmu.2022.943293
Anti-inflammatory and antioxidant effects of mesenchymal and hematopoietic stem cells in a rheumatoid arthritis rat model.
Abdelmawgoud Hanan,Saleh Asmaa
Advances in clinical and experimental medicine : official organ Wroclaw Medical University
BACKGROUND:Mesenchymal stem cells (MSCs) are of increased importance because of their capacity to counteract inflammation and suppress host immune responses. OBJECTIVES:The aim of the study was to compare the effectiveness of MSCs and hematopoietic stem cells (HSCs) in the treatment of rheumatoid arthritis (RA). MATERIAL AND METHODS:Paw swelling was assessed by measuring the thickness of the hind paws using a caliper. Cytokines - interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), and IL-10 - and rheumatoid factor (RF) were measured using enzyme-linked immunosorbent assay (ELISA) kits. Oxidative stress biomarkers - malondialdehyde (MDA) and reduced glutathione (GSH) were assessed. Nuclear factor-kappaB (NF-κB) was detected by the western blot technique. Toll-like receptor-2 (TLR-2), matrix metalloproteinase-3 (MMP-3) and cartilage oligomeric matrix protein-1 (COMP-1) gene expression were assessed by the real-time quantitative analysis. Mesenchymal stem cells were isolated from the bone marrow (BM) of rats and HSCs were isolated from human umbilical cord blood (UCB). RESULTS:Paw edema, RA score, RF, cytokine assay, antioxidant state, NF-κB, TLR-2, MMP3, and COMP-1 showed improvement in the group that received MSCs compared to the group that received HSCs and the group that received methotrexate. CONCLUSIONS:Mesenchymal stem cells are very effective in reducing RA inflammation; they are superior to HSC and methotrexate treatment. Mesenchymal stem cells could become a better therapeutic opportunity for the treatment of RA.
10.17219/acem/73720
Bone marrow derived mesenchymal stem cells therapy for rheumatoid arthritis - a concise review of past ten years.
Molecular biology reports
Rheumatoid arthritis is an autoimmune disorder characterized by swelling in synovial joints and erosion of bones. The disease is normally treated with conventional drugs which provide only temporary relief to the symptoms. Over the past few years, mesenchymal stromal cells have become the center of attention for treating this disease due to their immuno-modulatory and anti-inflammatory characteristics. Various studies on treatment of rheumatoid arthritis by using these cells have shown positive outcomes in terms of reduction in the level of pain as well as improvement of the function and structure of joints. Mesenchymal stromal cells can be derived from multiple sources, however, the ones derived from bone marrow are considered most beneficial for treating several disorders including rheumatoid arthritis on account of being safer and more effective. This review summarizes all the preclinical and clinical studies which were conducted over the last ten years for therapy of rheumatoid arthritis utilizing these cells. The literature was reviewed using the terms "mesenchymal stem/stromal cells and rheumatoid arthritis'' and "bone marrow derived mesenchymal stromal cells and therapy of rheumatoid arthritis''. Data was extracted to enable the readers to have access to the most relevant information regarding advancement in therapeutic potential of these stromal cells. Additionally, this review will also help in fulfilling any gap in current knowledge of readers about the outcome of using these cells in animal models, cell line and in patients suffering from rheumatoid arthritis and other autoimmune disorders as well.
10.1007/s11033-023-08277-9
Mesenchymal Stem Cells Improve Rheumatoid Arthritis Progression by Controlling Memory T Cell Response.
Luque-Campos Noymar,Contreras-López Rafael A,Jose Paredes-Martínez María,Torres Maria Jose,Bahraoui Sarah,Wei Mingxing,Espinoza Francisco,Djouad Farida,Elizondo-Vega Roberto Javier,Luz-Crawford Patricia
Frontiers in immunology
In the last years, mesenchymal stem cell (MSC)-based therapies have become an interesting therapeutic opportunity for the treatment of rheumatoid arthritis (RA) due to their capacity to potently modulate the immune response. RA is a chronic autoimmune inflammatory disorder with an incompletely understood etiology. However, it has been well described that peripheral tolerance defects and the subsequent abnormal infiltration and activation of diverse immune cells into the synovial membrane, are critical for RA development and progression. Moreover, the imbalance between the immune response of pro-inflammatory and anti-inflammatory cells, in particular between memory Th17 and memory regulatory T cells (Treg), respectively, is well admitted to be associated to RA immunopathogenesis. In this context, MSCs, which are able to alter the frequency and function of memory lymphocytes including Th17, follicular helper T (Tfh) cells and gamma delta (γδ) T cells while promoting Treg cell generation, have been proposed as a candidate of choice for RA cell therapy. Indeed, given the plasticity of memory CD4 T cells, it is reasonable to think that MSCs will restore the balance between pro-inflammatory and anti-inflammatory memory T cells populations deregulated in RA leading to prompt their therapeutic function. In the present review, we will discuss the role of memory T cells implicated in RA pathogenesis and the beneficial effects exerted by MSCs on the phenotype and functions of these immune cells abnormally regulated in RA and how this regulation could impact RA progression.
10.3389/fimmu.2019.00798
Rheumatoid arthritis: Recent advances on its etiology, role of cytokines and pharmacotherapy.
Alam Javaid,Jantan Ibrahim,Bukhari Syed Nasir Abbas
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
An autoimmune disease is defined as a clinical syndrome resulted from an instigation of both T cell and B cell or individually, in the absence of any present infection or any sort of distinguishable cause. Clonal deletion of auto reactive cells remains the central canon of immunology for decades, keeping the role of T cell and B cell aside, which are actually the guards to recognize the entry of foreign body. According to NIH, 23.5 million Americans are all together affected by these diseases. They are rare, but with the exception of RA. Rheumatoid arthritis is chronic and systemic autoimmune response to the multiple joints with unknown ethology, progressive disability, systemic complications, early death and high socioeconomic costs. Its ancient disease with an old history found in North American tribes since 1500 BCE, but its etiology is yet to be explored. Current conventional and biological therapies used for RA are not fulfilling the need of the patients but give only partial responses. There is a lack of consistent and liable biomarkers of prognosis therapeutic response, and toxicity. Rheumatoid arthritis is characterized by hyperplasic synovium, production of cytokines, chemokines, autoantibodies like rheumatoid factor (RF) and anticitrullinated protein antibody (ACPA), osteoclastogensis, angiogenesis and systemic consequences like cardiovascular, pulmonary, psychological, and skeletal disorders. Cytokines, a diverse group of polypeptides, play critical role in the pathogenesis of RA. Their involvement in autoimmune diseases is a rapidly growing area of biological and clinical research. Among the proinflammatory cytokines, IL-1α/β and TNF-α trigger the intracellular molecular signalling pathway responsible for the pathogenesis of RA that leads to the activation of mesenchymal cell, recruitment of innate and adaptive immune system cells, activation of synoviocytes which in term activates various mediators including tumour necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6) and interleukin-8 (IL-8), resulting in inflamed synovium, increase angiogenesis and decrease lymphangiogensis. Their current pharmacotherapy should focus on their three phases of progression i.e. prearthritis phase, transition phase and clinical phase. In this way we will be able to find a way to keep the balance between the pro and anti-inflammatory cytokines that is believe to be the dogma of pathogenesis of RA. For this we need to explore new agents, whether from synthetic or natural source to find the answers for unresolved etiology of autoimmune diseases and to provide a quality of life to the patients suffering from these diseases specifically RA.
10.1016/j.biopha.2017.05.055
Mesenchymal Stem/Stromal Cells for Rheumatoid Arthritis Treatment: An Update on Clinical Applications.
Lopez-Santalla Mercedes,Fernandez-Perez Raquel,Garin Marina I
Cells
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease that affects the lining of the synovial joints leading to stiffness, pain, inflammation, loss of mobility, and erosion of joints. Its pathogenesis is related to aberrant immune responses against the synovium. Dysfunction of innate and adaptive immunity, including dysregulated cytokine networks and immune complex-mediated complement activation, are involved in the progression of RA. At present, drug treatments, including corticosteroids, antirheumatic drugs, and biological agents, are used in order to modulate the altered immune responses. Chronic use of these drugs may cause adverse effects to a significant number of RA patients. Additionally, some RA patients are resistant to these therapies. In recent years, mesenchymal stem/stromal cell (MSCs)-based therapies have been largely proposed as a novel and promising stem cell therapeutic approach in the treatment of RA. MSCs are multipotent progenitor cells that have immunomodulatory properties and can be obtained and expanded easily. Today, nearly one hundred studies in preclinical models of RA have shown promising trends for clinical application. Proof-of-concept clinical studies have demonstrated satisfactory safety profile of MSC therapy in RA patients. The present review discusses MSC-based therapy approaches with a focus on published clinical data, as well as on clinical trials, for treatment of RA that are currently underway.
10.3390/cells9081852
The Outcome of Stem Cell-Based Therapies on the Immune Responses in Rheumatoid Arthritis.
Roudsari Peyvand Parhizkar,Alavi-Moghadam Sepideh,Rezaei-Tavirani Mostafa,Goodarzi Parisa,Tayanloo-Beik Akram,Sayahpour Forough Azam,Larijani Bagher,Arjmand Babak
Advances in experimental medicine and biology
Rheumatoid arthritis as a common autoimmune inflammatory disorder with unknown etiology can affect 0.5-1% of adults in developed countries. It involves more than just the patient's joints and can be accompanied by several comorbidities and affect cardiovascular, pulmonary, and some other systems of the human body. Although cytokine-mediated pathways are mentioned to have a central role in RA pathogenesis, adaptive and innate immune systems and intracellular signaling pathways all have important roles in this process. Non-steroidal anti-inflammatory drugs, glucocorticoids, conventional disease-modifying anti-rheumatic drugs, and biological agents are some mentioned medications used for RA. They are accompanied by some adverse effects and treatment failures which elucidates the needing for novel and more powerful therapeutic approaches. Stem cell-based therapies and their beneficial effects on therapeutic processes of different diseases have been founded so far. They can be an alternative and promising therapeutic approach for RA, too; due to their effects on immune responses of the disease. This review, besides some explanations about RA characteristics, addresses the outcome of the stem cell-based therapies including mesenchymal stem cell transplantation and hematopoietic stem cell transplantation for RA and explains their effects on the disease improvement.
10.1007/5584_2020_581
High dose therapy and autologous hemopoietic stem cell transplantation in rheumatoid arthritis--the feasibility of phase III trials.
Snowden J
The Journal of rheumatology. Supplement
If a niche is to be established for autografting in the treatment of severe rheumatoid arthritis (RA), investigators should have the common goal of providing higher levels of evidence. Autografting in RA can be envisaged only for severe RA that has resisted all safer available treatments, and given the relatively large numbers necessary for statistical power in randomized studies, investigators will need to work together. This article summarizes the current literature and discusses practical issues relating to future trials.