Abstract:Research on mesenchymal stem cells (MSCs) starts from the earliest assumption that cells derived from the bone marrow have the ability to repair tissues. Several scientists have since documented the crucial role of bone marrow-derived MSCs (BM-MSCs) in processes such as embryonic bone and cartilage formation, adult fracture and tissue repair, and immunomodulatory activities in therapeutic applications. In addition to BM-MSCs, several sources of MSCs have been reported to possess tissue repair and immunoregulat… Show more
“…[52][53][54][55] costimulatory molecules associated with T cell activation. 56 UC-MSCs significantly reduce inflammation by extensively downregulating inflammatory products or cytotoxic mediators that act on immune cells and increase the level of the anti-inflammatory cytokine IL-10. 57 In addition to suppressing the immune response, UC-MSCs induce the production of IL-10-secreting regulatory T cells (Tregs) during local inflammation.…”
Section: Reduction In the Inflammatory Responsementioning
confidence: 99%
“…Our previous study was registered at ClinicalTrials.gov (NCT01547091), 8 been demonstrated for the clinical treatment of RA. Additionally, we conducted prospective phase I/II studies in 10 juvenile idiopathic arthritis (JIA) children 56 less than 17 years of age and 64 RA patients 7 aged 18 to 64 years. The patients were treated with a 40 mL of a UC-MSC suspension product (2 × 10 7 cells/20 mL) via intravenous injection.…”
Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology with a high rate of disability. Traditional treatments for RA remain a challenging issue. For example, nonsteroidal anti-inflammatory drugs (NSAIDs) have no therapeutic effects on joint destruction, and the prominent side effects include gastrointestinal symptoms. RA is characterized by recurrence and bone attrition. Therefore, regenerative medicine and the use of umbilical cord mesenchymal stem cell (UC-MSC) therapies have recently emerged as potential options. UC-MSCs are multifunctional stem cells that are present in neonatal umbilical cord tissue and can differentiate into many kinds of cells, which have broad clinical application prospects in the tissue engineering of bone, cartilage, muscle, tendon, ligament, nerve, liver, endothelium, and myocardium. Moreover, UC-MSCs have advantages, such as convenient collection of materials and no ethical disputes; thus, these cells have attracted increasing attention from researchers. However, there are few clinical studies regarding UC-MSC therapy for RA. In this paper, we will review traditional drugs for RA treatment and then focus on UC-MSC therapy for RA, including preclinical and clinical UC-MSC applications for RA patients in the context of regenerative medicine. Finally, we will summarize the challenges and perspectives of UC-MSCs as a potential therapeutic strategy for RA. This review will help to design and discover more potent and efficacious treatments for RA patients and aid in advancing this class of cell therapy.
“…[52][53][54][55] costimulatory molecules associated with T cell activation. 56 UC-MSCs significantly reduce inflammation by extensively downregulating inflammatory products or cytotoxic mediators that act on immune cells and increase the level of the anti-inflammatory cytokine IL-10. 57 In addition to suppressing the immune response, UC-MSCs induce the production of IL-10-secreting regulatory T cells (Tregs) during local inflammation.…”
Section: Reduction In the Inflammatory Responsementioning
confidence: 99%
“…Our previous study was registered at ClinicalTrials.gov (NCT01547091), 8 been demonstrated for the clinical treatment of RA. Additionally, we conducted prospective phase I/II studies in 10 juvenile idiopathic arthritis (JIA) children 56 less than 17 years of age and 64 RA patients 7 aged 18 to 64 years. The patients were treated with a 40 mL of a UC-MSC suspension product (2 × 10 7 cells/20 mL) via intravenous injection.…”
Rheumatoid arthritis (RA) is an autoimmune disease of unknown etiology with a high rate of disability. Traditional treatments for RA remain a challenging issue. For example, nonsteroidal anti-inflammatory drugs (NSAIDs) have no therapeutic effects on joint destruction, and the prominent side effects include gastrointestinal symptoms. RA is characterized by recurrence and bone attrition. Therefore, regenerative medicine and the use of umbilical cord mesenchymal stem cell (UC-MSC) therapies have recently emerged as potential options. UC-MSCs are multifunctional stem cells that are present in neonatal umbilical cord tissue and can differentiate into many kinds of cells, which have broad clinical application prospects in the tissue engineering of bone, cartilage, muscle, tendon, ligament, nerve, liver, endothelium, and myocardium. Moreover, UC-MSCs have advantages, such as convenient collection of materials and no ethical disputes; thus, these cells have attracted increasing attention from researchers. However, there are few clinical studies regarding UC-MSC therapy for RA. In this paper, we will review traditional drugs for RA treatment and then focus on UC-MSC therapy for RA, including preclinical and clinical UC-MSC applications for RA patients in the context of regenerative medicine. Finally, we will summarize the challenges and perspectives of UC-MSCs as a potential therapeutic strategy for RA. This review will help to design and discover more potent and efficacious treatments for RA patients and aid in advancing this class of cell therapy.
“…Previous studies have indicated that the CD39+ CD8+ Tregs subset played a crucial role in regulating immune homeostasis, preventing excessive immune responses, and controlling autoimmune diseases by producing inhibitory cytokines and regulatory receptors ( 47 , 49 ). Some studies have shown that SLE patients often have limited function or reduced numbers of Tregs ( 50 – 52 ). However, there is controversy regarding the quantity of Tregs in SLE research.…”
BackgroundThe effect of immune cells on autoimmune diseases (ADs) complicated by non-Hodgkin lymphoma (NHL) has been widely recognized, but a causal relationship between regulatory T cell (Treg) immune traits and ADs complicated by NHL remains debated.MethodsAggregate data for 84 Treg-related immune traits were downloaded from the Genome-Wide Association Study (GWAS) catalog, and GWAS data for diffuse large B-cell lymphoma (DLBCL; n=315243), follicular lymphoma (FL; n=325831), sjögren’s syndrome (SS; n=402090), rheumatoid arthritis (RA; n=276465), dermatopolymyositis (DM; n=311640), psoriasis (n=407876), atopic dermatitis (AD; n=382254), ulcerative colitis (UC; n=411317), crohn’s disease(CD; n=411973) and systemic lupus erythematosus (SLE; n=307587) were downloaded from the FinnGen database. The inverse variance weighting (IVW) method was mainly used to infer any causal association between Treg-related immune traits and DLBCL, FL, SS, DM, RA, Psoriasis, AD, UC, CD and SLE, supplemented by MR-Egger, weighted median, simple mode, and weighted mode. Moreover, we performed sensitivity analyses to assess the validity of the causal relationships.ResultsThere was a potential genetic predisposition association identified between CD39+ CD8br AC, CD39+ CD8br % T cell, and the risk of DLBCL (OR=1.51, p<0.001; OR=1.25, p=0.001) (adjusted FDR<0.1). Genetic prediction revealed potential associations between CD25++ CD8br AC, CD28- CD25++ CD8br % T cell, CD39+ CD8br % CD8br, and the risk of FL (OR=1.13, p=0.022; OR=1.28, p=0.042; OR=0.90, p=0.016) (adjusted FDR>0.1). Furthermore, SLE and CD exhibited a genetically predicted potential association with the CD39+ CD8+ Tregs subset. SS and DM were possibly associated with an increase in the quantity of the CD4+ Tregs subset; RA may have reduced the quantity of the CD39+ CD8+ Tregs subset, although no causal relationship was identified. Sensitivity analyses supported the robustness of our findings.ConclusionsThere existed a genetically predicted potential association between the CD39+ CD8+ Tregs subset and the risk of DLBCL, while SLE and CD were genetically predicted to be potentially associated with the CD39+ CD8+ Tregs subset. The CD39+ CD8+ Tregs subset potentially aided in the clinical diagnosis and treatment of SLE or CD complicated by DLBCL.
“…The results of studies have also indicated that MSCs can ameliorate the RA through different mechanisms such as suppression of Th17 cells, reduction of inflammatory cytokines, and up-regulation of Treg cells (Fig. 2 ) [ 44 ]. Fig.…”
The autoimmune diseases are associated with the host immune system, chronic inflammation, and immune reaction against self-antigens, which leads to the injury and failure of several tissues. The onset of autoimmune diseases is related to unbalanced immune homeostasis. Mesenchymal stem cells (MSCs) are multipotent cells which have capability to self-renew and differentiate into various cell types that exert a critical role in immunomodulation and regenerative therapy. Under the certain condition in vitro, MSCs are able to differentiate into multiple lineage such as osteoblasts, adipocytes, and neuron-like cells. Consequently, MSCs have a valuable application in cell treatment. Accordingly, in this review we present the last observations of researches on different MSCs and their efficiency and feasibility in the clinical treatment of several autoimmune disorders including rheumatoid arthritis, type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, inflammatory bowel disease, autoimmune liver disease, and Sjogren’s syndrome.
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